Silicone hydrogel lenses with water-rich surfaces

ABSTRACT

The invention is related to a hydrated silicone hydrogel contact lens having a layered structural configuration: a lower water content silicone hydrogel core (or bulk material) completely covered with a layer of a higher water content hydrogel totally or substantially free of silicone. A hydrated silicone hydrogel contact lens of the invention possesses high oxygen permeability for maintaining the corneal health and a soft, water-rich, lubricious surface for wearing comfort.

This application is a continuation of application Ser. No. 15/730,773filed 12 Oct. 2017, which is a continuation of application Ser. No.15/202,759 filed 6 Jul. 2016, now U.S. Pat. No. 9,816,009, which is acontinuation of application Ser. No. 14/967,733 filed 14 Dec. 2015, nowU.S. Pat. No. 9,411,171, which is a continuation of application Ser. No.14/564,660 filed 9 Dec. 2014, now U.S. Pat. No. 9,244,200, which is acontinuation of application Ser. No. 13/900,136 filed 22 May 2013, nowU.S. Pat. No. 8,939,577, which is a continuation of application Ser. No.13/193,653 filed 29 Jul. 2011, now U.S. Pat. No. 8,480,227, which claimsthe benefits under 35 USC § 119 (e) of U.S. provisional application Nos.61/369,102 filed 30 Jul. 2010 and 61/448,478 filed 2 Mar. 2011,incorporated by reference in their entireties.

The present invention generally relates to an ophthalmic device,especially a silicone hydrogel contact lens which has a lens structuralconfiguration creating a water content gradient and comprises: asilicone hydrogel bulk material having a water content (designated asWC_(SiHy)) of from about 10% to about 70% by weight and an outer surfacelayer that has a thickness of about 0.1 to about 20 μm and completelycovers the silicone hydrogel bulk material and is made of a hydrogelmaterial totally or substantially free of silicone and having a higherwater content characterized by a water-swelling ratio of at least about100% if WC_(SiHy)≤45% or by a water-swelling ratio of at least about[120·WC_(SiHy)/(1−WC_(SiHy))]% if WC_(SiHy)>45%, as measured by AFM witha cross section of the silicone hydrogel contact lens in fully hydratedstate.

BACKGROUND

Silicone hydrogel (SiHy) contact lenses are widely used for correctingmany different types of vision deficiencies. They are made of ahydrated, crosslinked polymeric material that contains silicone and acertain amount of water within the lens polymer matrix at equilibrium.According to the FDA's contact lens classification, hydrogel contactlenses are generally classified into two main categories: low watercontent contact lenses (containing less than 50% of water) and highwater content contact lenses (containing greater than 50% of water). ForSiHy contact lenses, high oxygen permeability, which is required for acontact lens to have minimal adverse effects upon corneal health, isachieved by incorporating silicone, not by increasing water content, inthe crosslinked polymeric material. As a result, unlike conventionalhydrogel contact lenses, SiHy contact lenses can have a low watercontent while still having a relatively high oxygen permeability (Dk),for example, Focus® Night & Day® from CIBA Vision Corporation (ca. 23.5%H₂O and Dk˜140 Barrers; Air Optix® from CIBA Vision Corporation (ca. 33%H₂O and Dk˜110 Barrers); PureVision® from Bausch & Lomb (ca. 36% H₂O andDk˜100 Barrers); Acuvue® Oasys® from Johnson & Johnson (ca. 38% H₂O,Dk˜105 Barrers); Acuvue® Advance® from Johnson & Johnson (ca. 47% H₂O,Dk˜65 Barrers); Acuvue® TruEye™ from Johnson & Johnson (ca. 46% H₂O,Dk˜100 Barrers); Biofinity® from CooperVision (ca. 48% H₂O, Dk˜128Barrers); Avaira™ from CooperVision (ca. 46% H₂O, Dk˜100 Barrers); andPremiO™ from Menicon (ca. 40% H₂O, Dk˜129 Barrers).

Water in a SiHy contact lens can provide the desirable softness thatenable a SiHy lens to be worn for sufficiently long periods of time andprovides patients with the benefits including adequate initial comfort(i.e., immediately after lens insertion), relatively short period ofadapting time required for a patient to become accustomed to them,and/or proper fit. Higher water content would be desirable for providingSiHy contact lenses with biocompatibility and comfort. But, there is alimit to the amount of water (believed to be 80%) that a SiHy contactlens can contain while still possessing sufficient mechanical strengthand rigidity required for a contact lens, like conventional hydrogelcontact lenses. Moreover, high water content could also have undesiredconsequences. For instance, oxygen permeability of a SiHy contact lenscould be compromised by increasing water content. Further, high watercontent in a SiHy lens could result in greater in-eye dehydration andconsequently dehydration-induced wearing discomfort, because a SiHycontact lens with a high water content could deplete the limited supplyof tears (water) of the eye. It is believed that in-eye dehydration maybe derived from evaporation (i.e., water loss) at the anterior surfaceof the contact lens and such water loss is primarily controlled by waterdiffusion through a lens from the posterior surface to the anteriorsurface, and that the rate of diffusion is closely proportional to thewater content of the lens bulk material at equilibrium (L. Jones et al.,Contact Lens & Anterior Eye 25 (2002) 147-156, herein incorporated byreference in its entirety).

Incorporation of silicone in a contact lens material also hasundesirable effects on the biocompatibility of the contact lens, becausesilicone is hydrophobic and has great tendency to migrate onto the lenssurface being exposed to air. As a result, a SiHy contact lens willgenerally require a surface modification process to eliminate orminimize the exposure of silicone of the contact lens and to maintain ahydrophilic surface, including, for example, various plasma treatments(e.g., Focus® Night & Day® and Air Optix® from CIBA Vision Corporation;PureVision® from Bausch & Lomb; and PremiO™ from Menicon); internalwetting agents physically and/or chemically embedded in the SiHy polymermatrix (e.g., Acuvue® Oasys®, Acuvue® Advance® and Acuvue® TruEye™ fromJohnson & Johnson; Biofinity® and Avaira™ from CooperVision). Althoughsurface modification techniques used in the commercial SiHy lensproduction may provide fresh (unused) SiHy lenses with adequatelyhydrophilic surfaces, a SiHy lenses worn in the eye may have dry spotsand/or hydrophobic surface areas created due to air exposure, shearingforces of the eyelids, silicone migration, and/or partial failure toprevent silicone from exposure. Those dry spots and/or hydrophobicsurface areas are non-wettable and susceptible to adsorbing lipids orproteins from the ocular environment and may adhere to the eye, causingpatient discomfort.

Therefore, there are still needs for SiHy contact lenses withhydrophilic surfaces that have a persistent hydrophilicity, wettability,and lubricity that can be maintained in the eye throughout the entireday.

SUMMARY OF THE INVENTION

The present invention can satisfy the needs for SiHy contact lenses withhydrophilic surfaces that have a persistent surface hydrophilicity,surface wettability and surface lubricity in the eye throughout theentire day.

In one aspect, the invention provides a hydrated silicone hydrogelcontact lens which comprises: an anterior (convex) surface and anopposite posterior (concave) surface; and a layered structuralconfiguration from the anterior surface to the posterior surface,wherein the layered structural configuration includes an anterior outerhydrogel layer, an inner layer of a silicone hydrogel material, and aposterior outer hydrogel layer, wherein the silicone hydrogel materialhas an oxygen permeability (Dk) of at least about 50, preferably atleast about 60, more preferably at least about 70, even more preferablyat least about 90 barrers, most preferably at least about 110 Barrers,and a first water content (designated as WC_(SiHy)) of from about 10% toabout 70%, preferably from about 10% to about 65%, more preferably fromabout 10% to about 60%, even more preferably from about 15% to about55%, most preferably from about 15% to about 50% by weight, wherein theanterior and posterior outer hydrogel layers are substantially uniformin thickness and merge at the peripheral edge of the contact lens tocompletely enclose the inner layer of the silicone hydrogel material,wherein the anterior and posterior outer hydrogel layers independent ofeach other have a second water content higher than WC_(SiHy), ascharacterized either by having a water-swelling ratio (designated asWSR) of at least about 100% (preferably at least about 150%, morepreferably at least about 200%, even more preferably at least about250%, most preferably at least about 300%) if WC_(SiHy)≤45%, or byhaving a water-swelling ratio of at least about[120·WC_(SiHy)/(1−WC_(SiHy))]% (preferably[130·WC_(SiHy)/(1−WC_(SiHy))], more preferably[140·WC_(SiHy)/(1−WC_(SiHy))]%, even more preferably[150·WC_(SiHy)/(1−WC_(SiHy))]%) if WC>45%, wherein the thickness of eachof the anterior and posterior outer hydrogel layers is from about 0.1 μmto about 20 μm, preferably from about 0.25 μm to about 15 μm, morepreferably from about 0.5 μm to about 12.5 μm, even more preferably fromabout 1 μm to about 10 μm (as measured with atomic force microscopyacross a cross section from the posterior surface to the anteriorsurface of the silicone hydrogel contact lens in fully hydrated state).

In another aspect, the invention provides a hydrated silicone hydrogelcontact lens. A hydrated silicone hydrogel contact lens of the inventioncomprises: a silicone hydrogel material as bulk material, an anteriorsurface and an opposite posterior surface; wherein the contact lens hasan oxygen transmissibility of at least about 40, preferably at leastabout 60, more preferably at least about 80, even more preferably atleast about 110 barrers/mm, and a cross-sectional surface-modulusprofile which comprises, along a shortest line between the anterior andposterior surfaces on the surface of a cross section of the contactlens, an anterior outer zone including and near the anterior surface, aninner zone including and around the center of the shortest line, and aposterior outer zone including and near the posterior surface, whereinthe anterior outer zone has an average anterior surface modulus(designated as SM_(Ant) ) while the posterior outer zone has an averageposterior surface modulus (designated as SM_(post) ), wherein the innerzone has an average inner surface modulus (designated as SM_(Inner) ),wherein at least one of

$\frac{\overset{\_}{{SM}_{Inner}} - \overset{\_}{{SM}_{Post}}}{\overset{\_}{{SM}_{Inner}}} \times 100\%\mspace{14mu}{and}\mspace{14mu}\frac{\overset{\_}{{SM}_{Inner}} - \overset{\_}{{SM}_{Ant}}}{\overset{\_}{{SM}_{Inner}}} \times 100\%$is at least about 20%, preferably at least about 25%, more preferably atleast about 30%, even more preferably at least about 35%, mostpreferably at least about 40%.

In a further aspect, the invention provides a hydrated silicone hydrogelcontact lens. A hydrated silicone hydrogel contact lens of the inventioncomprises: a silicone hydrogel material as bulk material, an anteriorsurface and an opposite posterior surface; wherein the contact lens has(1) an oxygen transmissibility of at least about 40, preferably at leastabout 60, more preferably at least about 80, even more preferably atleast about 110 barrers/mm, and (2) a surface lubricity characterized byhaving a critical coefficient of friction (designated as CCOF) of about0.046 or less, preferably about 0.043 or less, more preferably about0.040 or less, wherein the anterior and posterior surfaces have a lowsurface concentration of negatively-charged groups including carboxylicacid groups as characterized by attracting at most about 200, preferablyat most about 160, more preferably at most about 120, even morepreferably at most about 90, most preferably at most about 60positively-charged particles in positively-charged-particles-adhesiontest.

These and other aspects of the invention including various preferredembodiments in any combination will become apparent from the followingdescription of the presently preferred embodiments. The detaileddescription is merely illustrative of the invention and does not limitthe scope of the invention, which is defined by the appended claims andequivalents thereof. As would be obvious to one skilled in the art, manyvariations and modifications of the invention may be effected withoutdeparting from the spirit and scope of the novel concepts of thedisclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically depicts a sectional view of the structuralconfiguration of a SiHy contact lens according to a preferred embodimentof the invention.

FIG. 2 schematically depicts a sectional view of the structuralconfiguration of a SiHy contact lens according to another preferredembodiment of the invention.

FIG. 3 shows the fluorescence intensity profiles across the crosssections of a SiHy contact lens in a con-focal laser fluorescencemicroscopy.

FIG. 4 shows the SEM (scanning electron microscopy) images of a SiHycontact lens of the invention in a freeze-dried state.

FIG. 5 schematically illustrates the set up of the inclined plate methodaccording to a preferred embodiment.

FIG. 6 shows optical microscopic images of contact lenses havingdifferent coatings thereon after being immersed in a dispersion ofpositively charged particles (DOWEX™ 1×4 20-50 Mesh resins).

FIG. 7 schematically illustrates how to mount vertically in a metalclamp a cross-section piece of a SiHy contact lens of the invention forAFM testing.

FIG. 8 shows the AFM (atomic force microscopy) image of a portion of across section of a SiHy contact lens in fully hydrated state (inphosphate buffered saline, pH˜7.3) according to a preferred embodimentof the invention.

FIG. 9 shows a cross sectional surface modulus profile of a SiHy contactlens of the invention in fully hydrated state (in phosphate-bufferedsaline, pH˜7.3), along two shortest line between the anterior andposterior surfaces on the surface of a cross section of a SiHy contactlens, according to a preferred embodiment of the invention asrepresented approximately by the plots of the cantilever deflection asfunction of the distance.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Reference now will be made in detail to the embodiments of theinvention. It will be apparent to those skilled in the art that variousmodifications, variations and combinations can be made in the presentinvention without departing from the scope or spirit of the invention.For instance, features illustrated or described as part of oneembodiment, can be used on another embodiment to yield a still furtherembodiment. Thus, it is intended that the present invention cover suchmodifications, variations and combinations as come within the scope ofthe appended claims and their equivalents. Other objects, features andaspects of the present invention are disclosed in or are obvious fromthe following detailed description. It is to be understood by one ofordinary skill in the art that the present discussion is a descriptionof exemplary embodiments only, and is not intended as limiting thebroader aspects of the present invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Generally, the nomenclatureused herein and the laboratory procedures are well known and commonlyemployed in the art. Conventional methods are used for these procedures,such as those provided in the art and various general references. Wherea term is provided in the singular, the inventors also contemplate theplural of that term. The nomenclature used herein and the laboratoryprocedures described below are those well known and commonly employed inthe art.

As used in this application, the term “silicone hydrogel contact lens”refers to a contact lens comprising a silicone hydrogel material.

As used in this application, the term “hydrogel” or “hydrogel material”refers to a crosslinked polymeric material which is not water-solubleand can contains at least 10% by weight of water within its polymermatrix when fully hydrated.

As used in this application, the term “non-silicone hydrogel” refers toa hydrogel that is theoretically free of silicon.

As used in this application, the term “silicone hydrogel” refers to ahydrogel containing silicone. A silicone hydrogel typically is obtainedby copolymerization of a polymerizable composition comprising at leastone silicone-containing vinylic monomer or at least onesilicone-containing vinylic macromer or at least one silicone-containingprepolymer having ethylenically unsaturated groups.

As used in this application, the term “vinylic monomer” refers to acompound that has one sole ethylenically unsaturated group and can bepolymerized actinically or thermally.

As used in this application, the term “olefinically unsaturated group”or “ethylenically unsaturated group” is employed herein in a broad senseand is intended to encompass any groups containing at least one >C═C<group. Exemplary ethylenically unsaturated groups include withoutlimitation (meth)acryloyl

or other C═C containing groups.

As used in this application, the term “(meth)acrylamide” refers tomethacrylamide and/or acrylamide.

As used in this application, the term “(meth)acrylate” refers tomethacrylate and/or acrylate.

As used in this application, the term “hydrophilic vinylic monomer”refers to a vinylic monomer which as a homopolymer typically yields apolymer that is water-soluble or can absorb at least 10 percent byweight water.

As used in this application, the term “hydrophobic vinylic monomer”refers to a vinylic monomer which as a homopolymer typically yields apolymer that is insoluble in water and can absorb less than 10 percentby weight water.

As used in this application, the term “macromer” or “prepolymer” refersto a medium and high molecular weight compound or polymer that containstwo or more ethylenically unsaturated groups. Medium and high molecularweight typically means average molecular weights greater than 700Daltons.

As used in this application, the term “crosslinker” refers to a compoundhaving at least two ethylenically unsaturated groups. A “crosslinkingagent” refers to a crosslinker having a molecular weight of about 700Daltons or less.

As used in this application, the term “polymer” means a material formedby polymerizing/crosslinking one or more monomers or macromers orprepolymers.

As used in this application, the term “molecular weight” of a polymericmaterial (including monomeric or macromeric materials) refers to theweight-average molecular weight unless otherwise specifically noted orunless testing conditions indicate otherwise.

As used in this application, the term “amino group” refers to a primaryor secondary amino group of formula —NHR′, where R′ is hydrogen or aC₁-C₂₀ unsubstituted or substituted, linear or branched alkyl group,unless otherwise specifically noted.

As used in this application, the term “epichlorohydrin-functionalizedpolyamine” or “epichlorohydrin-functionalized polyamidoamine” refers toa polymer obtained by reacting a polyamine or polyamidoamine withepichlorohydrin to convert all or a substantial percentage of aminegroups of the polyamine or polyamidoamine into azetidinium groups.

As used in this application, the term “azetidinium group” refers to apositively charged group of

As used in this application, the term “thermally-crosslinkable” inreference to a polymeric material or a functional group means that thepolymeric material or the functional group can undergo a crosslinking(or coupling) reaction with another material or functional group at arelatively-elevated temperature (from about 40° C. to about 140° C.),whereas the polymeric material or functional group cannot undergo thesame crosslinking reaction (or coupling reaction) with another materialor functional group at room temperature (i.e., from about 22° C. toabout 28° C., preferably from about 24° C. to about 26° C., inparticular at about 25° C.) to an extend detectable (i.e., greater thanabout 5%) for a period of about one hour.

As used in this application, the term “phosphorylcholine” refers to azwitterionic group of

in which n is an integer of 1 to 5 and R₁, R₂ and R₃ independently ofeach other are C₁-C₈ alkyl or C₁-C₈ hydroxyalkyl.

As used in this application, the term “reactive vinylic monomer” refersto a vinylic monomer having a carboxyl group or an amino group (i.e., aprimary or secondary amino group).

As used in this application, the term “non-reactive hydrophilic vinylicmonomer” refers to a hydrophilic vinylic monomer which is free of anycarboxyl group or amino group (i.e., primary or secondary amino group).A non-reactive vinylic monomer can include a tertiary or quaterniumamino group.

As used in this application, the term “water-soluble” in reference to apolymer means that the polymer can be dissolved in water to an extentsufficient to form an aqueous solution of the polymer having aconcentration of up to about 30% by weight at room temperature (definedabove).

As used in this application, the term “water contact angle” refers to anaverage water contact angle (i.e., contact angles measured by SessileDrop method), which is obtained by averaging measurements of contactangles.

As used in this application, the term “intactness” in reference to acoating on a SiHy contact lens is intended to describe the extent towhich the contact lens can be stained by Sudan Black in a Sudan Blackstaining test described in Example 1. Good intactness of the coating ona SiHy contact lens means that there is practically no Sudan Blackstaining of the contact lens.

As used in this application, the term “durability” in reference to acoating on a SiHy contact lens is intended to describe that the coatingon the SiHy contact lens can survive a digital rubbing test.

As used in this application, the term “surviving a digital rubbing test”or “surviving a durability test” in reference to a coating on a contactlens means that after digitally rubbing the lens according to aprocedure described in Example 1, water contact angle on the digitallyrubbed lens is still about 100 degrees or less, preferably about 90degrees or less, more preferably about 80 degrees or less, mostpreferably about 70 degrees or less.

The intrinsic “oxygen permeability”, Dk, of a material is the rate atwhich oxygen will pass through a material. As used in this application,the term “oxygen permeability (Dk)” in reference to a hydrogel (siliconeor non-silicone) or a contact lens means a measured oxygen permeability(Dk) which is corrected for the surface resistance to oxygen flux causedby the boundary layer effect according to the procedures shown inExamples hereinafter. Oxygen permeability is conventionally expressed inunits of barrers, where “barrer” is defined as [(cm³oxygen)(mm)/(cm²)(sec)(mm Hg)]×10⁻¹⁰.

The “oxygen transmissibility”, Dk/t, of a lens or material is the rateat which oxygen will pass through a specific lens or material with anaverage thickness of t [in units of mm] over the area being measured.Oxygen transmissibility is conventionally expressed in units ofbarrers/mm, where “barrers/mm” is defined as [(cm³ oxygen)/(cm²)(sec)(mmHg)]×10⁻⁹.

The “ion permeability” through a lens correlates with the lonofluxDiffusion Coefficient. The lonoflux Diffusion Coefficient, D (in unitsof [mm²/min]), is determined by applying Fick's law as follows:D=−n′/(A×dc/dx)where n′=rate of ion transport [mol/min]; A=area of lens exposed [mm²];dc=concentration difference [mol/L]; dx=thickness of lens [mm].

As used in this application, the term “ophthalmically compatible” refersto a material or surface of a material which may be in intimate contactwith the ocular environment for an extended period of time withoutsignificantly damaging the ocular environment and without significantuser discomfort.

As used in this application, the term “ophthalmically safe” with respectto a packaging solution for sterilizing and storing contact lenses isintended to mean that a contact lens stored in the solution is safe fordirect placement on the eye without rinsing after autoclave and that thesolution is safe and sufficiently comfortable for daily contact with theeye via a contact lens. An ophthalmically-safe packaging solution afterautoclave has a tonicity and a pH that are compatible with the eye andis substantially free of ocularly irritating or ocularly cytotoxicmaterials according to international ISO standards and U.S. FDAregulations.

As used in this application, the term “cross section” of a SiHy contactlens refers to a lens section obtained by cutting through the lens witha knife or cutting tool at an angle substantially normal to either ofthe anterior and posterior surfaces of the lens. A person skilled in theart knows well to cut manually (i.e., hand cut), or with CryostaMicrotome or with a lath, a contact lens to obtain a cross section ofthe contact lens. A resultant cross section of a contact lens can bepolished by using ion etching or similar techniques.

The terms “surface modulus”, “surface softness”, “surface elasticmodulus”, “surface Young' modulus”, or surface compression modulus areused interchangeably in this application to means a nanomechnicalproperty (elastic property) which is measured by atomic force microscopy(AFM) on a surface of a material or a cross section of a contact lens infully hydrated state (in phosphate buffered solution, pH˜7.3±0.2), usingcontact mode, nanoindentation method, Peakforce QNM method, or HarmonicForce method, as known to a person skilled in the art. Jan Domke andManfred Radmacher reported that the elastic properties of thin films canbe measured with AMF (Langmuir 1998, 14, 3320-3325, herein incorporatedby reference in its entirety). AFM nanoindentation can be performedaccording to the experimental protocol described by Gonzalez-Méijome JM, Almeida J B and Parafita M A in Microscopy: Science, Technology,Applications and Education, “Analysis of Surface Mechanical Propertiesof Unworn and Worn Silicone Hydrogel Contact Lenses UsingNanoindentation with AFM”, pp 554-559, A. Mendez-Vilas and J. Diaz(Eds.), Formatex Research Center, Badajoz, Spain (2010), hereinincorporated by reference in its entirety. It is noted that the surfaceof a cross section of a contact lens, not the anterior or posteriorsurface of a contact lens (as done by Gonzalez-Méijome J M, Almeida J Band Parafita M A in their article), is analyzed using nanoindentationwith AFM. Nanoindentation method, Peakforce QNM method and HarmonicForce method are described in the paper by Kim Sweers, et al. inNanoscale Research Letters 2011, 6:270, entitled “Nanomechanicalproperties of a-synuclein amyloid fibrils: a comparative study bynanoindentation, harmonic force microscopy, and Peakforce QNM” (hereinincorporated by reference in its entirety. It is also understood thatwhen measurements of surface elastic modulus is carried out with AFMacross a cross section of a fully hydrated SiHy contact lens from theanterior surface to the bulk or from the bulk to the posterior surface(or vice versa), a surface modulus profile across a cross section of acontact lens can be established along a shortest line between theanterior and posterior surfaces on the surface of the cross section ofthe contact lens. It is further understood that as a good approximation,any experimentally and directly measured quantity can be used torepresent the surface modulus so long as the measured quantity isproportional to the surface modulus.

As used in this application, the term “anterior outer hydrogel layer” inreference to a SiHy contact lens of the invention means a hydrogel layerthat includes the anterior surface of the contact lens, is substantiallyuniform in thickness (i.e., variation in thickness is not more thanabout 10% from the average thickness of that layer), and has an averagethickness of at least about 0.1 μm. The “average thickness” of ananterior outer hydrogel layer is simply referred to as the “thickness ofan anterior outer hydrogel layer” in this application.

As used in this application, the term “posterior outer hydrogel layer”in reference to a SiHy contact lens of the invention means a hydrogellayer that includes the posterior surface of the contact lens, issubstantially uniform in thickness (i.e., variation in thickness is notmore than about 10% from the average thickness of that layer), and hasan average thickness of at least about 0.1 μm. The “average thickness”of a posterior outer hydrogel layer is simply referred to as the“thickness of a posterior outer hydrogel layer” in this application.

As used in this application, the term “inner layer” in reference to aSiHy contact lens of the invention means a layer that includes a centralcurved plane (which divides the contact lens into two parts, onecontaining the anterior surface and the other containing the posteriorsurface) and has a variable thickness.

As used in this application, the term “crosslinked coating” or “hydrogelcoating” interchangeably is used to describe a crosslinked polymericmaterial having a three-dimensional network that can contain water whenfully hydrated. The three-dimensional network of a crosslinked polymericmaterial can be formed by crosslinking of two or more linear or branchedpolymers through crosslinkages.

As used in this application, the term “water-swelling ratio,” inreference to an anterior or posterior outer hydrogel layer of a hydrogelmaterial of a SiHy contact lens of the invention, means a valuedetermined with AFM according to

${WSR} = {\frac{L_{Wet}}{L_{Dry}} \times 100\%}$in which WSR is the water-swelling ratio of one of the anterior andposterior outer hydrogel layer, L_(Wet) is the average thickness of thatouter hydrogel layer of the SiHy contact lens in fully hydrated state asmeasured with AFM on a cross section of the SiHy contact lens in fullyhydrated state (i.e., in phosphate buffered solution, pH˜7.3±0.2), andL_(Dry) is the average thickness of that outer hydrogel layer of theSiHy contact lens in dry state as measured with AFM on a cross sectionof the SiHy contact lens in dry state (dried without preserving theporosity of the hydrogel material, e.g., vacuum dried) and insubstantially dry atmosphere. It is believed that a water-swelling ratioof each outer hydrogel layer (of a SiHy contact lens of the invention)is proportional to the water content possessed by each outer hydrogellayer and a water-swelling ratio of at least about

$100\%\mspace{14mu}{or}\mspace{14mu}\frac{120 \cdot {WC}_{SiHy}}{1 - {WC}_{SiHy}}\%$(whichever is larger, WC_(SiHy) is the water content of the bulk (orinner layer of) silicone hydrogel material of a SiHy contact lens of theinvention) can be served as a good indicator of the nature of the outerhydrogel layers having a higher water content relative to the bulk (orinner layer of) silicone hydrogel material of a SiHy contact lens of theinvention.

As used in the this application, the term “reduced surface modulus”, inreference to either or both of the anterior and posterior outer hydrogellayers of a SiHy contact lens of the invention, is intended to mean avalue calculated based on the following equation

${RSM} = {\frac{\overset{\_}{{SM}_{inner}} - \overset{\_}{{SM}_{Outer}}}{\overset{\_}{{SM}_{Inner}}} \times 100\%}$In which RSM is the reduced modulus of the anterior or posterior outerhydrogel layer relative to the inner layer, SM_(Outer) is the averagesurface modulus of the posterior or anterior outer hydrogel layer, andSM_(Inner) is the average surface modulus of the inner layer. SM_(Outer)and SM_(Inner) are obtained from a cross-sectional surface modulusprofile of the SiHy contact lens in fully hydrated state (as measured byanalyzing surface mechanic properties, i.e., surface moduli of a crosssection of the fully hydrated SiHy contact lens using AFM), as describedabove. It is expected that the cross-sectional surface modulus profile(i.e., a graph of surface modulus vs. distance from one of the anteriorand posterior surfaces to the other surface along a shortest linebetween the anterior and posterior surfaces on the surface of a crosssection of a SiHy lens in fully hydrated state) should have at least twoouter zones (one including the anterior surface and the other includingthe posterior surface) and one inner zone (corresponding to the bulksilicone hydrogel material. The average surface modulus for the outerzone (i.e., outer hydrogel layer) is obtained by averaging all surfacemoduli in the outer zone excluding a region of about 1 to about 2microns between the outer zone and the inner zone (i.e., in and/or nearthe boundary region or transition zone).

A “critical coefficient of friction” is the tangent of the criticalangle which is the highest inclined angle of an inclined plate at whicha lens begins sliding on the inclined plate after being pushed, butstops, or takes longer than 10 seconds, before reaching the end. Theprocedures for determining the critical coefficient of friction (CCOF)are described in Example 29. It is believed that the criticalcoefficient of friction (CCOF) of a contact lens correlates with thesurface lubricity of that contact lens and can be used to quantify thesurface lubricity of a contact lens.

As used in this application, the “positively-charged-particles-adhesiontest” refers a test for characterizing the surface concentration ofnegatively-charged groups (e.g., carboxylic acid groups) of a hydratedSiHy contact lens. The positively-charged-particles-adhesion test isperformed as follows. An aqueous dispersion of DOWEX™ 1×4 20-50 Meshresins, which are spherical, Type I strong base resins(styrene/divinylbenzene copolymers containing N⁺(CH₃)₃Cl⁻ functionalgroups and 4% divinylbenzene) is prepared by dispersing a given amountof DOWEX™ 1×4 20-50 Mesh resins in a phosphate buffered saline (pH˜7.3)to have a resin concentration of 5% by weight and then mixed well byshaking or stirring or vortexing at approximately 1000 rpm for 10seconds. Hydrated silicone hydrogel contact lenses are immersed in theaqueous dispersion of DOWEX™ 1×4 20-50 Mesh resins prepared above andstirred vortexed at an rpm of about 1000-1100 for 1 about minute,followed by rinsing with DI water and vortexing in DI water for about 1minute. Then, the lenses are placed in water in glass Petri dishes andimages of lenses are taken with Nikon optical microscope, using bottomlighting. The number of positively-charged particles adhered onto thesurface of each lens can be counted. The number of positively-chargedparticles adhered onto the surface of the lens is proportional to thesurface concentration of negatively-charged groups of a contact lens.

As used in this application, the term “carboxylic acid content”, inreference to the crosslinked coating or an outer hydrogel layer of aSiHy contact lens of the invention, means the weight percentage ofcarboxylic group (COOH) based on the weight of the crosslinked coatingor the outer hydrogel layer of the SiHy contact lens. The carboxylicacid content of a crosslinked coating or an outer hydrogel layer can beestimated theoretically based on the composition of starting materialsfor making the crosslinked coating or the outer hydrogel layer and onthe carboxylic acid content of each starting materials.

The invention is related to a SiHy contact lens having a layeredstructural configuration and unique water gradient from inside tooutside of the SiHy contact lens: a lower water content siliconehydrogel core (or bulk material) completely covered with an outer(surface) hydrogel layer having a higher water content and adequatethickness (at least about 0.1 μm) and being substantially free ofsilicone (preferably totally free of silicone); and the water content ofthe outer hydrogel layer being at least about 1.2 folds (or 120%),preferably at least about 1.3 folds (or 130%), more preferably at leastabout 1.4 folds (or 140%), even more preferably at least about 1.5 folds(150%), most preferably at least about 2 folds (or 200%) of the watercontent of the bulk material. FIG. 1 schematically illustrates a SiHycontact lens having a layered structural configuration, according to apreferred embodiment. In accordance with this preferred embodiment ofthe invention, the SiHy contact lens 100 has an anterior surface (orfront curve or convex surface) 101 and an opposite posterior surface (orbase curve or concave surface) 102 which is rest on the cornea of theeye when worn by a user. The SiHy contact lens 100 comprises an inner(or middle) layer 110 and two outer layers 120. The inner layer 110 isthe bulk material of SiHy contact lens 100 and has a 3-dimensional shapevery close to the SiHy contact lens 100. The inner layer 110 ispreferably made of a lower water content silicone hydrogel. The twoouter layers 120, substantially identical to each other, aresubstantially uniform in thickness and made of a hydrogel materialsubstantially free of silicone (preferably totally free of silicone)having a higher water content relative to that of the inner layer 110.The two outer layers 120 merge at the peripheral edge 103 of the contactlens 100 and cover completely the inner layer 110.

A SiHy contact lens with a layered structural configuration of theinvention can offer several advantages over contact lenses in the priorart. First, such a SiHy contact lens can still possess high oxygenpermeability, which is required to maintain the corneal health of theeye. Second, because the inner layer (bulk material) provides bulkmechanical strength and rigidity required for a contact lens, the outerhydrogel layers may have no limit with respect to the water content andcan contain water as much as possible. As such, the outer hydrogellayers can provide the contact lens with a skin super-enriched withwater or a water content gradient in the lens structural configuration(highest water content in the region near and including the lens surfaceand lowest water content in the lens core). Third, a SiHy contact lenswith a layered structural configuration of the invention may have lowin-eye dehydration, may cause less dryness sensation in the eye, andconsequently can have enhanced end-day wearing comfort. It is believedthat the inner layer (i.e., the bulk material of the lens) with lowwater content will control (limit) the rate of water diffusion through alens from the posterior surface to the anterior surface and in turn theevaporation (water loss) at the anterior surface of the lens. It is alsobelieved that a layered structural configuration of the invention maycreate an inward water concentration gradient (i.e., the water contentdecreasing as going inwardly from the anterior surface toward the lenscore), which is unfavorable for water diffusion through a lens from theposterior surface to the anterior surface based on Fick's laws ofdiffusion. Fourth, a SiHy contact lens with a layered structuralconfiguration of the invention may provide high biocompatibility,because water is highly biocompatible with the tear and because highwater content (e.g., preferably >75% H₂O) in the outer hydrogel layersis located in and nears the anterior and posterior surfaces with whichthe eye is in direct contact and where the biocompatibility counts most.Fifth, high water content in the outer hydrogel layers with adequatethickness may provide a SiHy contact lens with a highly soft surface,i.e., a “water cushion.” Sixth, a SiHy contact lens with a layeredstructural configuration of the invention may have a highly lubricioussurface. It is believed that the outer hydrogel layer with much higherwater content and with adequate thickness would provide a “water-loving”surface which can attract tears to be spread on the lens surface. It isbelieved that the outer hydrogel layer with much higher softness thanthat of the bulk lens material (the inner layer) may be very susceptibleto deformation under pressure (i.e., shearing forces of the eyelids) andmay provide elastohydrodynamic lubrication when such a SiHy contact lensis worn in the eye. Seventh, a layered structural configuration in aSiHy contact lens of the invention may prevent silicone from exposure.It is believed that the three dimensional mesh network (i.e., polymericmatrix) of the outer hydrogel layers with adequate thickness can sheathsilicone and prevent silicone from migrating onto the lens surface.Eighth, a SiHy contact lens of the invention can have a low surfaceconcentration of negatively-charged groups (e.g., carboxylic acidgroups) and is less susceptible to high debris adhesion during patienthandling and high protein adhesion during wearing (a majority ofproteins in tears is believed to be positively charged).

In one aspect, the invention provides a hydrated silicone hydrogelcontact lens which comprises: an anterior (convex) surface and anopposite posterior (concave) surface; and a layered structuralconfiguration from the anterior surface to the posterior surface,wherein the layered structural configuration includes an anterior outerhydrogel layer, an inner layer of a silicone hydrogel material, and aposterior outer hydrogel layer, wherein the silicone hydrogel materialhas an oxygen permeability (Dk) of at least about 50, preferably atleast about 60, more preferably at least about 70, even more preferablyat least about 90, most preferably at least about 110 barrers, and afirst water content (designated as WC_(SiHy)) of from about 10% to about70%, preferably from about 10% to about 65%, more preferably from about10% to about 60%, even more preferably from about 15% to about 55%, mostpreferably from about 15% to about 50% by weight, wherein the anteriorand posterior outer hydrogel layers are substantially uniform inthickness and merge at the peripheral edge of the contact lens tocompletely enclose the inner layer of the silicone hydrogel material,and wherein the anterior and posterior outer hydrogel layers independentof each other have a second water content higher than WC_(SiHy), ascharacterized either by having a water-swelling ratio of at least about100% (preferably at least about 150%, more preferably at least about200%, even more preferably at least about 250%, most preferably at leastabout 300%) if WC_(SiHy)≤45%, or by having a water-swelling ratio of atleast about

$\frac{120 \cdot {WC}_{SiHy}}{1 - {WC}_{SiHy}}\%\;{\quad\mspace{14mu}{\quad{\text{(}{preferably}\mspace{14mu}\frac{130 \cdot {WC}_{SiHy}}{1 - {WC}_{SiHy}}{\%\mspace{14mu},}}}}$more preferably

${\frac{140 \cdot {WC}_{SiHy}}{1 - {WC}_{SiHy}}\%}\mspace{14mu},$even more preferably

$\frac{150 \cdot {WC}_{SiHy}}{1 - {WC}_{SiHy}}\%\left. \quad \right)$if WC_(SiHy)>45%, wherein the thickness of each outer hydrogel layer isfrom about 0.1 μm to about 20 μm, preferably from about 0.25 μm to about15 μm, more preferably from about 0.5 μm to about 12.5 μm, even morepreferably from about 1 μm to about 10 μm (as measured with atomic forcemicroscopy across a cross section from the posterior surface to theanterior surface of the silicone hydrogel contact lens in fully hydratedstate). Preferably, the anterior and posterior surfaces have a lowsurface concentration of negatively-charged groups (e.g., carboxylicacid groups) as characterized by attracting at most at most about 200,preferably at most about 160, more preferably at most about 120, evenmore preferably at most about 90, most preferably at most about 60positively-charged particles in positively-charged-particles-adhesiontest. Also preferably, the hydrated silicone hydrogel contact lens has asurface lubricity characterized by having a critical coefficient offriction (designated as CCOF) of about 0.046 or less, preferably about0.043 or less, more preferably about 0.040 or less.

In accordance with the invention, the inner layer of a SiHy contact lensis practically the bulk material of the lens. It can be derived directlyfrom a preformed SiHy contact lens in a surface modification processwhere two outer hydrogel layers are applied and attached directly and/orindirectly onto the preformed SiHy contact lenses. A preformed SiHycontact lens can be any commercial SiHy lens, such as, one of thosedescribed above. Alternatively, a preformed SiHy can be made accordingto any methods well known to a person skilled in the art. For example,preformed contact lenses can be produced in a conventional “spin-castingmold,” as described for example in U.S. Pat. No. 3,408,429, or by thefull cast-molding process in a static form, as described in U.S. Pat.Nos. 4,347,198; 5,508,317; 5,583,463; 5,789,464; and 5,849,810, or bylathe cutting of silicone hydrogel buttons as used in making customizedcontact lenses. In cast-molding, a lens formulation typically isdispensed into molds and cured (i.e., polymerized and/or crosslinked) inmolds for making contact lenses. For production of preformed SiHycontact lenses, a SiHy lens formulation for cast-molding or spin-castmolding or for making SiHy rods used in lathe-cutting of contact lensesgenerally comprises at least one components selected from the groupconsisting of a silicone-containing vinylic monomer, asilicone-containing vinylic macromer, a silicone-containing prepolymer,a hydrophilic vinylic monomer, a hydrophobic vinylic monomer, acrosslinking agent (a compound having a molecular weight of about 700Daltons or less and containing at least two ethylenically unsaturatedgroups), a free-radical initiator (photoinitiator or thermal initiator),a hydrophilic vinylic macromer/prepolymer, and combination thereof, aswell known to a person skilled in the art. A SiHy contact lensformulation can also comprise other necessary components known to aperson skilled in the art, such as, for example, a UV-absorbing agent, avisibility tinting agent (e.g., dyes, pigments, or mixtures thereof),antimicrobial agents (e.g., preferably silver nanoparticles), abioactive agent, leachable lubricants, leachable tear-stabilizingagents, and mixtures thereof, as known to a person skilled in the art.Resultant preformed SiHy contact lenses then can be subjected toextraction with an extraction solvent to remove unpolymerized componentsfrom the resultant lenses and to hydration process, as known by a personskilled in the art. In addition, a preformed SiHy contact lens can be acolored contact lens (i.e., a SiHy contact lens having at least onecolored patterns printed thereon as well known to a person skilled inthe art).

Any suitable silicone-containing vinylic monomers can be used in theinvention. Examples of preferred silicone-containing vinylic monomersinclude without limitationN-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide,N-[tris(dimethylpropylsiloxy)-silylpropyl]-(meth)acrylamide,N-[tris(dimethylphenylsiloxy)silylpropyl] (meth)acrylamide,N-[tris(dimethylethylsiloxy)silylpropyl] (meth)acrylamide,N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)-2-methylacrylamide;N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)acrylamide;N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]-2-methylacrylamide; N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl] acrylamide;N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)-2-methylacrylamide;N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)acrylamide;N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methylacrylamide;N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]acrylamide;N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy) propyl]-2-methylacrylamide;N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide;N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methylacrylamide;N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide;3-methacryloxy propylpentamethyldisiloxane,tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS),(3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane),(3-methacryloxy-2-hydroxypropyloxy)propyltris(trimethylsiloxy)silane,3-methacryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane,N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silylcarbamate,3-(trimethylsilyl)propylvinyl carbonate,3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane,3-[tris(trimethylsiloxy)silyl]propylvinyl carbamate,3-[tris(trimethylsiloxy)silyl] propyl allyl carbamate,3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate,t-butyldimethyl-siloxyethyl vinyl carbonate; trimethylsilylethyl vinylcarbonate, and trimethylsilylmethyl vinyl carbonate). Most preferredsiloxane-containing (meth)acrylamide monomers of formula (1) areN-[tris(trimethylsiloxy)silylpropyl]acrylamide, TRIS,N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide, orcombinations thereof.

A class of preferred silicone-containing vinylic monomers or macromersis polysiloxane-containing vinylic monomers or macromers. Examples ofsuch polysiloxane-containing vinylic monomers or macromers aremonomethacrylated or monoacrylated polydimethylsiloxanes of variousmolecular weight (e.g., mono-3-methacryloxypropyl terminated, mono-butylterminated polydimethylsiloxane ormono-(3-methacryloxy-2-hydroxypropyloxy)propyl terminated, mono-butylterminated polydimethylsiloxane); dimethacrylated or diacrylatedpolydimethylsiloxanes of various molecular weight; vinylcarbonate-terminated polydimethylsiloxanes; vinyl carbamate-terminatedpolydimethylsiloxane; vinyl terminated polydimethylsiloxanes of variousmolecular weight; methacrylamide-terminated polydimethylsiloxanes;acrylamide-terminated polydimethylsiloxanes; acrylate-terminatedpolydimethylsiloxanes; methacrylate-terminated polydimethylsiloxanes;bis-3-methacryloxy-2-hydroxypropyloxypropyl polydimethylsiloxane;N,N,N′,N′-tetrakis(3-methacryloxy-2-hydroxypropyl)-alpha,omega-bis-3-aminopropyl-polydimethylsiloxane;polysiloxanylalkyl (meth)acrylic monomers; siloxane-containing macromerselected from the group consisting of Macromer A, Macromer B, MacromerC, and Macromer D described in U.S. Pat. No. 5,760,100 (hereinincorporated by reference in its entirety); the reaction products ofglycidyl methacrylate with amino-functional polydimethylsiloxanes;hydroxyl-functionalized siloxane-containing vinylic monomers ormacromers; polysiloxane-containing macromers disclosed in U.S. Pat. Nos.4,136,250, 4,153,641, 4,182,822, 4,189,546, 4,343,927, 4,254,248,4,355,147, 4,276,402, 4,327,203, 4,341,889, 4,486,577, 4,543,398,4,605,712, 4,661,575, 4,684,538, 4,703,097, 4,833,218, 4,837,289,4,954,586, 4,954,587, 5,010,141, 5,034,461, 5,070,170, 5,079,319,5,039,761, 5,346,946, 5,358,995, 5,387,632, 5,416,132, 5,451,617,5,486,579, 5,962,548, 5,981,675, 6,039,913, and 6,762,264 (hereincorporated by reference in their entireties); polysiloxane-containingmacromers disclosed in U.S. Pat. Nos. 4,259,467, 4,260,725, and4,261,875 (herein incorporated by reference in their entireties). Di andtriblock macromers consisting of polydimethylsiloxane andpolyalkyleneoxides could also be of utility. For example, one might usemethacrylate end cappedpolyethyleneoxide-block-polydimethylsiloxane-block-polyethyleneoxide toenhance oxygen permeability. Suitable monofunctionalhydroxyl-functionalized siloxane-containing vinylic monomers/macromersand suitable multifunctional hydroxyl-functionalized siloxane-containingvinylic monomers/macromers are commercially available from Gelest, Inc,Morrisville, Pa.

Another class of preferred silicone-containing macromers issilicon-containing prepolymers comprising hydrophilic segments andhydrophobic segments. Any suitable of silicone-containing prepolymerswith hydrophilic segments and hydrophobic segments can be used in theinvention. Examples of such silicone-containing prepolymers includethose described in commonly-owned U.S. Pat. Nos. 6,039,913, 7,091,283,7,268,189 and 7,238,750, 7,521,519; commonly-owned US patent applicationpublication Nos. US 2008-0015315 A1, US 2008-0143958 A1, US 2008-0143003A1, US 2008-0234457 A1, US 2008-0231798 A1, and commonly-owned US patentapplication Nos. 61/180,449 and 61/180,453; all of which areincorporated herein by references in their entireties.

Examples of preferred hydrophilic vinylic monomers areN,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA),2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,1-n-propyl-3-methylene-2-pyrrolidone,1-n-propyl-5-methylene-2-pyrrolidone,1-isopropyl-3-methylene-2-pyrrolidone,1-isopropyl-5-methylene-2-pyrrolidone,1-n-butyl-3-methylene-2-pyrrolidone,1-tert-butyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl methacrylate(HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate,hydroxypropyl methacrylate (HPMA), trimethylammonium 2-hydroxypropylmethacrylate hydrochloride, aminopropyl methacrylatehydrochloride, dimethylaminoethyl methacrylate (DMAEMA), glycerolmethacrylate (GMA), N-vinyl-2-pyrrolidone (NVP), allyl alcohol,vinylpyridine, a C₁-C₄-alkoxy polyethylene glycol (meth)acrylate havinga weight average molecular weight of up to 1500, methacrylic acid,N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide,N-vinyl-N-methyl acetamide, allyl alcohol, N-vinyl caprolactam, andmixtures thereof.

Examples of preferred hydrophobic vinylic monomers includemethylacrylate, ethyl-acrylate, propylacrylate, isopropylacrylate,cyclohexylacrylate, 2-ethylhexylacrylate, methylmethacrylate,ethylmethacrylate, propylmethacrylate, vinyl acetate, vinyl propionate,vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride,vinylidene chloride, acrylonitrile, 1-butene, butadiene,methacrylonitrile, vinyl toluene, vinyl ethyl ether,perfluorohexylethyl-thio-carbonyl-aminoethylmethacrylate, isobornylmethacrylate, trifluoroethyl methacrylate, hexafluoro-isopropylmethacrylate, hexafluorobutyl methacrylate.

Examples of preferred cross-linking agents include without limitationtetraethyleneglycol diacrylate, triethyleneglycol diacrylate,ethyleneglycol diacylate, diethyleneglycol diacrylate,tetraethyleneglycol dimethacrylate, triethyleneglycol dimethacrylate,ethyleneglycol dimethacylate, diethyleneglycol dimethacrylate,trimethylopropane trimethacrylate, pentaerythritol tetramethacrylate,bisphenol A dimethacrylate, vinyl methacrylate, ethylenediaminedimethyacrylamide, ethylenediamine diacrylamide, glyceroldimethacrylate, triallyl isocyanurate, triallyl cyanurate,allylmethacrylate, allylmethacrylate,1,3-bis(methacrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane,N,N′-methylenebisacrylamide, N,N′-methylenebismethacrylamide,N,N′-ethylenebisacrylamide, N,N′-ethylenebismethacrylamide,1,3-bis(N-methacrylamidopropyl)-1,1,3,3-tetrakis-(trimethylsiloxy)disiloxane,1,3-bis(methacrylamidobutyl)-1,1,3,3-tetrakis(trimethylsiloxy)-disiloxane,1,3-bis(acrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane,1,3-bis(methacryloxyethylureidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane,and combinations thereof. A preferred cross-linking agent istetra(ethyleneglycol) diacrylate, tri(ethyleneglycol) diacrylate,ethyleneglycol diacrylate, di(ethyleneglycol) diacrylate,methylenebisacrylamide, triallyl isocyanurate, or triallyl cyanurate.The amount of a cross-linking agent used is expressed in the weightcontent with respect to the total polymer and is preferably in the rangefrom about 0.05% to about 4%, and more preferably in the range fromabout 0.1% to about 2%.

Examples of suitable thermal initiators include, but are not limited to,2,2′-azobis (2,4-dimethylpentanenitrile), 2,2′-azobis(2-methylpropanenitrile), 2,2′-azobis (2-methylbutanenitrile), peroxidessuch as benzoyl peroxide, and the like. Preferably, the thermalinitiator is 2,2′-azobis(isobutyronitrile) (AlBN).

Suitable photoinitiators are benzoin methyl ether, diethoxyacetophenone,a benzoylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone and Darocurand Irgacur types, preferably Darocur 1173® and Darocur 2959®. Examplesof benzoylphosphine initiators include2,4,6-trimethylbenzoyldiphenylophosphine oxide;bis-(2,6-dichlorobenzoyl)-4-N-propylphenylphosphine oxide; andbis-(2,6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. Reactivephotoinitiators which can be incorporated, for example, into a macromeror can be used as a special monomer are also suitable. Examples ofreactive photoinitiators are those disclosed in EP 632 329, hereinincorporated by reference in its entirety. The polymerization can thenbe triggered off by actinic radiation, for example light, in particularUV light of a suitable wavelength. The spectral requirements can becontrolled accordingly, if appropriate, by addition of suitablephotosensitizers.

Any suitable polymerizable UV-absorbing agents can be used in theinvention. Preferably, a polymerizable UV-absorbing agent comprises abenzotriazole-moiety or a benzophenone-moiety. Examples of preferredpolymerizable UV absorbers include without limitation2-(2-hydroxy-5-vinylphenyl)-2H-benzotriazole,2-(2-hydroxy-5-acrylyloxyphenyl)-2H-benzotriazole,2-(2-hydroxy-3-methacrylamido methyl-5-tert octylphenyl)benzotriazole,2-(2′-hydroxy-5′-methacrylamidophenyl)-5-chlorobenzotriazole,2-(2′-hydroxy-5′-methacrylamidophenyl)-5-methoxybenzotriazole,2-(2′-hydroxy-5′-methacryloxypropyl-3′-t-butyl-phenyl)-5-chlorobenzotriazole,2-(2′-hydroxy-5′-methacryloxyethylphenyl)benzotriazole,2-(2′-hydroxy-5′-methacryloxypropylphenyl)benzotriazole,2-hydroxy-4-acryloxy alkoxy benzophenone, 2-hydroxy-4-methacryloxyalkoxy benzophenone, allyl-2-hydroxybenzophenone,2-hydroxy-4-methacryloxy benzophenone.

The bioactive agent is any compound that can prevent a malady in the eyeor reduce the symptoms of an eye malady. The bioactive agent can be adrug, an amino acid (e.g., taurine, glycine, etc.), a polypeptide, aprotein, a nucleic acid, or any combination thereof. Examples of drugsuseful herein include, but are not limited to, rebamipide, ketotifen,olaptidine, cromoglycolate, cyclosporine, nedocromil, levocabastine,lodoxamide, ketotifen, or the pharmaceutically acceptable salt or esterthereof. Other examples of bioactive agents include2-pyrrolidone-5-carboxylic acid (PCA), alpha hydroxyl acids (e.g.,glycolic, lactic, malic, tartaric, mandelic and citric acids and saltsthereof, etc.), linoleic and gamma linoleic acids, and vitamins (e.g.,B5, A, B6, etc.).

Examples of leachable lubricants include without limitation mucin-likematerials (e.g., polyglycolic acid) and non-crosslinkable hydrophilicpolymers (i.e., without ethylenically unsaturated groups). Anyhydrophilic polymers or copolymers without any ethylenically unsaturatedgroups can be used as leachable lubricants. Preferred examples ofnon-crosslinkable hydrophilic polymers include, but are not limited to,polyvinyl alcohols (PVAs), polyamides, polyimides, polylactone, ahomopolymer of a vinyl lactam, a copolymer of at least one vinyl lactamin the presence or in the absence of one or more hydrophilic vinyliccomonomers, a homopolymer of acrylamide or methacrylamide, a copolymerof acrylamide or methacrylamide with one or more hydrophilic vinylicmonomers, polyethylene oxide (i.e., polyethylene glycol (PEG)), apolyoxyethylene derivative, poly-N—N-dimethylacrylamide, polyacrylicacid, poly 2 ethyl oxazoline, heparin polysaccharides, polysaccharides,and mixtures thereof. The weight-average molecular weight M_(w) of thenon-crosslinkable hydrophilic polymer is preferably from 5,000 to1,00,000.

Examples of leachable tear-stabilizing agents include, withoutlimitation, phospholipids, monoglycerides, diglycerides, triglycerides,glycolipids, glyceroglycolipids, sphingolipids, sphingo-glycolipids,fatty alcohols, fatty acids, mineral oils, and mixtures thereof.Preferably, a tear stabilizing agent is a phospholipid, a monoglyceride,a diglyceride, a triglyceride, a glycolipid, a glyceroglycolipid, asphingolipid, a sphingo-glycolipid, a fatty acid having 8 to 36 carbonatoms, a fatty alcohol having 8 to 36 carbon atoms, or a mixturethereof.

In accordance with the invention, a SiHy lens formulation can be asolution or a melt at a temperature from about 20° C. to about 85° C.Preferably, a polymerizable composition is a solution of all desirablecomponents in a suitable solvent, or a mixture of suitable solvents.

A SiHy lens formulation can be prepared by dissolving all of thedesirable components in any suitable solvent, such as, water, a mixtureof water and one or more organic solvents miscible with water, anorganic solvent, or a mixture of one or more organic solvents, as knownto a person skilled in the art.

Example of preferred organic solvents includes without limitation,tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycolmethyl ether, ethylene glycol n-butyl ether, ketones (e.g., acetone,methyl ethyl ketone, etc.), diethylene glycol n-butyl ether, diethyleneglycol methyl ether, ethylene glycol phenyl ether, propylene glycolmethyl ether, propylene glycol methyl ether acetate, dipropylene glycolmethyl ether acetate, propylene glycol n-propyl ether, dipropyleneglycol n-propyl ether, tripropylene glycol n-butyl ether, propyleneglycol n-butyl ether, dipropylene glycol n-butyl ether, tripropyleneglycol n-butyl ether, propylene glycol phenyl ether dipropylene glycoldimetyl ether, polyethylene glycols, polypropylene glycols, ethylacetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate,i-propyl lactate, methylene chloride, 2-butanol, 1-propanol, 2-propanol,menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol,3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol,2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol,tert-amyl alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol,3-methyl-3-pentanol, 1-methylcyclohexanol, 2-methyl-2-hexanol,3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol,2-methyl-2-heptanol, 2-methyl-2-octanol, 2-2-methyl-2-nonanol,2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol,4-methyl-4-heptanol, 3-methyl-3-octanol, 4-methyl-4-octanol,3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol,3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl-4-heptanol,4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol,1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol,3-hydroxy-3-methyl-1-butene, 4-hydroxy-4-methyl-1-cyclopentanol,2-phenyl-2-propanol, 2-methoxy-2-methyl-2-propanol2,3,4-trimethyl-3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol,2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol,1-ethoxy-2-propanol, 1-methyl-2-propanol, t-amyl alcohol, isopropanol,1-methyl-2-pyrrolidone, N,N-dimethylpropionamide, dimethyl formamide,dimethyl acetamide, dimethyl propionamide, N-methyl pyrrolidinone, andmixtures thereof.

Numerous SiHy lens formulations have been described in numerous patentsand patent applications published by the filing date of thisapplication. All of them can be used in obtaining a preformed SiHy lenswhich in turn becomes the inner layer of a SiHy contact lens of theinvention, so long as they will yield a SiHy material having a Dk andwater content specified above. A SiHy lens formulation for makingcommercial SiHy lenses, such as, lotrafilcon A, lotrafilcon B,balafilcon A, galyfilcon A, senofilcon A, narafilcon A, narafilcon B,comfilcon A, enfilcon A, asmofilcon A, filcon II 3, can also be used inmaking preformed SiHy contact lenses (the inner layer of a SiHy contactlens of the invention).

Lens molds for making contact lenses are well known to a person skilledin the art and, for example, are employed in cast molding or spincasting. For example, a mold (for cast molding) generally comprises atleast two mold sections (or portions) or mold halves, i.e. first andsecond mold halves. The first mold half defines a first molding (oroptical) surface and the second mold half defines a second molding (oroptical) surface. The first and second mold halves are configured toreceive each other such that a lens forming cavity is formed between thefirst molding surface and the second molding surface. The moldingsurface of a mold half is the cavity-forming surface of the mold and indirect contact with lens-forming material.

Methods of manufacturing mold sections for cast-molding a contact lensare generally well known to those of ordinary skill in the art. Theprocess of the present invention is not limited to any particular methodof forming a mold. In fact, any method of forming a mold can be used inthe present invention. The first and second mold halves can be formedthrough various techniques, such as injection molding or lathing.Examples of suitable processes for forming the mold halves are disclosedin U.S. Pat. No. 4,444,711 to Schad; U.S. Pat. No. 4,460,534 to Boehm etal.; U.S. Pat. No. 5,843,346 to Morrill; and U.S. Pat. No. 5,894,002 toBoneberger et al., which are also incorporated herein by reference.

Virtually all materials known in the art for making molds can be used tomake molds for making contact lenses. For example, polymeric materials,such as polyethylene, polypropylene, polystyrene, PMMA, Topas® COC grade8007-S10 (clear amorphous copolymer of ethylene and norbornene, fromTicona GmbH of Frankfurt, Germany and Summit, N.J.), or the like can beused. Other materials that allow UV light transmission could be used,such as quartz glass and sapphire.

In a preferred embodiment, reusable molds are used and thesilicone-hydrogel lens-forming composition is cured actinically under aspatial limitation of actinic radiation to form a SiHy contact lens.Examples of preferred reusable molds are those disclosed in U.S. patentapplication Ser. No. 08/274,942 filed Jul. 14, 1994, Ser. No. 10/732,566filed Dec. 10, 2003, Ser. No. 10/721,913 filed Nov. 25, 2003, and U.S.Pat. No. 6,627,124, which are incorporated by reference in theirentireties. Reusable molds can be made of quartz, glass, sapphire, CaF₂,a cyclic olefin copolymer (such as for example, Topas® COC grade8007-S10 (clear amorphous copolymer of ethylene and norbornene) fromTicona GmbH of Frankfurt, Germany and Summit, N.J., Zeonex® and Zeonor®from Zeon Chemicals LP, Louisville, Ky.), polymethylmethacrylate (PMMA),polyoxymethylene from DuPont (Delrin), Ultem® (polyetherimide) from G.E.Plastics, PrimoSpire®, etc.

In accordance with the invention, the silicone hydrogel (bulk material)of the inner layer has an oxygen permeability of at least about 50,preferably at least about 60, more preferably at least about 70, evenmore preferably at least about 90 barrers, most preferably at leastabout 110 Barrers. The silicone hydrogel material can also have a(first) water content WC_(SiHy) of from about 10% to about 70%,preferably from about 10% to about 65%, more preferably from about 10%to about 60%; even more preferably from about 15% to about 55%, mostpreferably from about 15% to about 50% by weight. The silicone hydrogelmaterial can further have a bulk elastic modulus or bulk Young Modulus(hereinafter the terms, “softness,” “elastic modulus,” and “Young'smodulus” are interchangeably used in this application to mean bulkelastic modulus if the term is not modified by the word “surface.”) offrom about 0.3 MPa to about 1.8 MPa, preferably from 0.4 MPa to about1.5 MPa, more preferably from about 0.5 MPa to about 1.2 MPa. The oxygenpermeability, elastic modulus and water content of the inner layer ofthe silicone hydrogel material of a SiHy contact lens of the inventioncan be determined by measuring the oxygen permeability, the elasticmodulus and water content of the preformed SiHy lens from which theinner layer is derived. It is understood that as a reasonableapproximation, the elastic modulus of a SiHy contact lens of theinvention can be considered to be the elastic modulus of the siliconehydrogel material of the inner layer, because of the much thinner outerhydrogel layers. A person skilled in the art knows well how to determinethe elastic modulus and water content of a silicone hydrogel material ora SiHy contact lens. For example, all commercial SiHy contact lenseshave reported values of elastic modulus and water content.

The two outer hydrogel layers of a SiHy contact lens of the inventionpreferably are substantially identical to each other and are acrosslinked coating which is applied onto a preformed SiHy contact lenshaving a desired Dk, water content, and bulk elastic modulus.

The layered structure configuration of a SiHy contact lens of theinvention can be established by analysis with atomic force microscopy(AFM) of a cross section of a SiHy contact lens in fully hydrated state(i.e., directly in water or a buffered saline) as described above andshown in Examples. The surface moduli of a cross section can becharacterized (imaged) with AFM (e.g., Force-Volume mode) in order tovisualize any changes in surface modulus from the posterior surface sideto the anterior surface side across the cross section. A significantchange (e.g., about 20% or greater, preferably about 30% or greater)observed in surface modulus (by examining the AFM image) over athickness of about 0.04 μm, preferably about 0.03 μm, more preferablyabout 0.02 μm, even more preferably about 0.01 μm along a shortest linebetween the anterior and posterior surfaces across a cross section ofthe SiHy contact lens in fully hydrated state indicates a transitionfrom one layer to a different layer. The average thickness of each outerhydrogel layer can be determined from the AFM image as well known to aperson skilled in the art.

The two outer hydrogel layers of a SiHy contact lens of the inventionare substantially uniform in thickness. They merge at the peripheraledge of the contact lens to completely enclose the inner layer of thesilicone hydrogel material. The thickness of each outer hydrogel layeris from about 0.1 μm to about 20 μm, preferably from about 0.25 μm toabout 15 μm, even more preferably from about 0.5 μm to about 12.5 μm,most preferably from about 1 μm to about 10 μm. The thickness of theouter hydrogel layers (or crosslinked coating) of a SiHy contact lens ofthe invention is determined by AFM analysis of a cross section of theSiHy contact lens in fully hydrated state as described above. In a morepreferred embodiment, the thickness of each outer hydrogel layer ispreferably at most about 30% (i.e., 30% or less), preferably at mostabout 20% (20% or less), more preferably at most about 10% (10% or less)of the center thickness of the SiHy contact lens in fully hydratedstate.

It is understood that the layered structure configuration of a SiHycontact lens of the invention can also be established qualitatively byanalysis with scanning electron microscopy (SEM) of a cross section ofthe freeze-dried SiHy contact lens as shown in Examples. SEM can showthe different compositions and/or structures of each layers of a crosssection of the SiHy contact lens in freeze-dried state. A significantchange (e.g., about 20% or greater, preferably about 30% or greater)observed in the compositions and/or a significant (visually noticeable)changes in structures (by examining the SEM image) over a thickness ofabout 0.04 μm, preferably about 0.03 μm, more preferably about 0.02 μm,even more preferably about 0.01 μm across a cross section of the SiHycontact lens in freeze-dried state indicates a transition from one layerto a different layer. However, the thickness value based on SEM analysisof a cross section of a SiHy lens in freeze-dried state is typicallylower than actual value because of collapse of the outer hydrogellayers, transition layer if applicable, and the inner layer after beingfreeze-dried.

In accordance with this aspect of the invention, the two outer hydrogellayers (the anterior and posterior outer hydrogel layers) of a SiHycontact lens of the invention comprise a (second) water content thatmust be higher than the (first) water content (WC_(SiHy)) of the innerlayer of the silicone hydrogel material and more specifically must be atleast about 1.2 folds (i.e., 120%) of the (first) water content(WC_(SiHy)) of the inner layer of the silicone hydrogel material. It isbelieved that the water-swelling ratio of each outer hydrogel layercorrelates with its water content and as a good approximation canrepresent reasonably the water content of the outer hydrogel layer. Inalternatively preferred embodiments, where the water content (WC_(SiHy))of the inner layer of the silicone hydrogel material is about 55% orless, the water-swelling ratio of each outer hydrogel layer is at leastabout 150%; where the water content (WC_(SiHy)) of the inner layer ofthe silicone hydrogel material is about 60% or less, the water-swellingratio of each outer hydrogel layer is at least about 200%; where thewater content (WC_(SiHy)) of the inner layer of the silicone hydrogelmaterial is about 65% or less, the water-swelling ratio of each outerhydrogel layer is at least about 250%; where the water content(WC_(SiHy)) of the inner layer of the silicone hydrogel material isabout 70% or less, the water-swelling ratio of each outer hydrogel layeris at least about 300%.

It is understood that the water content of the anterior and posteriorouter hydrogel layers (the crosslinked coating) can be determined moreaccurately according to the procedures described in Example 23.Alternatively, the water content of the two outer hydrogel layers (thecrosslinked coating) can be determined with an article comprising anon-water-absorbent thin substrate and a crosslinked coating thereon,wherein the crosslinked coating is applied onto the non-water-absorbentthin substrate according to the identical coating process for the SiHycontact lens under substantial identical conditions. The water contentof each outer hydrogel layer then can be determined based on thedifference between dry and hydrated weights of the article with thecrosslinked coating.

In accordance with the invention, each of the two outer hydrogel layersis substantially free of silicone, preferably totally free of silicone.However, it is well known that when X-ray photoelectron spectroscopy(XPS) is used to establish the presence or absence of silicon in theouter hydrogel layer (generally a probing depth of from 1.5 to 6 nm),samples are inevitably contaminated by the environmental silicon, asshown by the detection by XPS of silicon on the surface of samples whichare theoretically free of any silicon atom, such as, for example, apolyethylene sheet, a DAILIES® AquaComfortPlus™ contact lens from CIBAVISION Corporation or an ACUVUE® Moist from Johnson & Johnson (seeExample 21 below). As such, the term “substantially free of silicon” isused in this application to mean that a surface silicon atomicpercentage measured by XPS on a SiHy contact lens is less than about200%, preferably less than about 175%, more preferably less than about150%, even more preferably less than about 125% of the silicon atomicpercentage of a control sample known to be inherently (theoretically)free of silicon (e.g., a polyethylene sheet, a DAILIES® AquaComfortPlus™contact lens from CIBA VISION Corporation or an ACUVUE® Moist fromJohnson & Johnson). Alternatively, each outer hydrogel layer of a SiHycontact lens of the invention is substantially free of silicon, ascharacterized by having a silicon atomic percentage of about 5% or less,preferably about 4% or less, even more preferably about 3% or less, oftotal elemental percentage, as measured by XPS analysis of the contactlens in dried state. It is understood that a small percentage ofsilicone may be optionally (but preferably not) incorporated into thepolymer network of the outer hydrogel layer so long as it would notsignificantly deteriorate the surface properties (hydrophilicity,wettability, and/or lubricity) of a SiHy contact lens.

In a preferred embodiment, the anterior and posterior outer hydrogellayers (the crosslinked coating) have a crosslinking density (orcrosslink density) sufficient low to provide the crosslinked coating orthe outer hydrogel layers (i.e., the SiHy contact lens) with a highdigital-rubbing resistance as characterized by having no surfacecracking lines visible under dark field after the SiHy contact lens isrubbed between fingers. It is believed that digital-rubbing-inducedsurface cracking may reduce the surface lubricity and/or may not be ableprevent silicone from migrating onto the surface (exposure). Surfacecracking may also indicate excessive crosslinking density in the surfacelayers which may affect the surface elastic modulus. Preferably, thenon-silicone hydrogel material in the outer hydrogel layers (thecrosslinked coating) comprises crosslinkages derived from azetidiniumgroups in a thermally-induced coupling reaction.

In another preferred embodiment, the anterior and posterior surfaceshave a low surface concentration of negatively-charged groups includingcarboxylic acid groups as characterized by attracting at most at mostabout 200, preferably at most about 160, more preferably at most about120, even more preferably at most about 90, most preferably at mostabout 60 positively-charged particles inpositively-charged-particles-adhesion test. It is desirable to have aminimal surface concentration of negatively charged groups (e.g.,carboxylic acid groups) on a SiHy contact lens of the invention, becausecontact lenses with a high surface concentration of negatively chargedgroups (e.g., carboxylic acid groups) are susceptible to high debrisadhesion during patient handling, high protein adhesion during wearing(a majority of proteins in tears is believed to be positively charged),high deposition and accumulation of antimicrobials suchPolyhexamethylene Biguanide (PHMB) present in contact lens caresolutions. To have a low surface concentration of negatively chargedgroups (e.g., carboxylic acid groups), the anterior and posterior outerhydrogel layers should have a relatively low carboxylic acid content.Preferably the anterior and posterior outer hydrogel layers have acarboxylic acid content of about 20% by weight or less, preferably about15% by weight or less, even more preferably about 10% by weight or less,most preferably about 5% by weight or less.

In another preferred embodiment, a SiHy contact lens of the inventionhas a good surface lubricity characterized by having a criticalcoefficient of friction (designated as CCOF) of about 0.046 or less,preferably about 0.043 or less, more preferably about 0.040 or less.Alternatively, a SiHy contact lens of the invention preferably has alubricity better than ACUVUE OASYS or ACUVUE TruEye as measured in ablind test according to the lubricity evaluation procedures described inExample 1.

In another preferred embodiment, a SiHy contact lens of the inventionfurther comprises, in its layered structural configuration, twotransition layers of polymeric material(s), as schematically illustratedin FIG. 2. Each of the two transition layers 115 is located between theinner layer 110 and one of the two outer hydrogel layers 120. Eachtransition layer is substantially uniform in thickness. The thickness ofeach transition layer is at least about 0.05 μm, preferably from about0.05 μm to about 10 μm, more preferably from about 0.1 μm to about 7.5μm, even more preferably from about 0.15 μm to about 5 μm. Thetransition layers merge at the peripheral edge of the contact lens tocompletely enclose the inner layer of the silicone hydrogel material.The presence and thickness of the transition layers can be determinedpreferably by AFM analysis of a cross section of the SiHy contact lensin fully hydrated state as described above for the outer hydrogel layersand inner layers.

The two transition layers of a SiHy contact lens of the inventionessentially are a base (or primer) coating which is applied onto apreformed SiHy contact lens having a desired Dk, water content, and bulkelastic modulus, before the crosslinked coating (the outer hydrogellayers) is applied thereon. The transition layers (base coating)function to anchor/attach the outer hydrogel layers. Preferably, thetransition layers comprise a carboxyl (COOH)-containing polymer,preferably a homo or copolymer of acrylic acid or methacrylic acid orC₂-C₁₂ alkylacrylic acid. It is understood that the carboxyl-containingpolymer may penetrate into the bulk material and extend into the outerhydrogel layers. When such penetration into the inner layer of thesilicone hydrogel material occurs, each transition layer would comprisethe carboxyl-containing polymer and the silicone hydrogel which areintertwined together. It is also believed that the presence of thetransition layers, especially when comprising a carboxyl-containingpolymer, may provide a relatively-high water content over a thickerlayer and/or a water reservoir for the outer hydrogel layers, because ofthe high water-binding properties of carboxyl groups. Moreover, even ifthe transition layer may contain high carboxylic acid groups, it wouldhave a minimal adverse impact upon the surface concentration ofcarboxylic acid groups of the SiHy contact lens, because the surfaceconcentration of carboxylic acid groups is predominantly determined bythe outer hydrogel layers which fully cover the transition layer. Theouter hydrogel layers with a low surface concentration of carboxylicacid groups can prevent the deposition of positively-charged proteinsfrom the tears of a patient wearing the lens.

In another preferred embodiment, the anterior and posterior outerhydrogel layers independent of each other have a reduced surface modulusof at least about 20%, preferably at least about 25%, more preferably atleast about 30%, even more preferably at least about 35%, mostpreferably at least about 40%, relative to the inner layer.

The anterior and posterior outer hydrogel layers are preferably made ofthe same or substantially identical material(s) (preferably totally freeof silicone) and can be formed by applying and crosslinking awater-soluble and crosslinkable hydrophilic polymeric material onto apreformed SiHy contact lens that comprises amino and/or carboxyl groupson and/or near the surface of the contact lens, or a base coatingcomprising amino and/or carboxyl groups, wherein the preformed SiHycontact lens becomes the inner layer after crosslinking.

In accordance with the invention, a preformed SiHy contact lens caneither inherently comprise or be modified to comprise amino groupsand/or carboxyl groups on and/or near its surface.

Where a preformed SiHy contact lens inherently comprises amino groupsand/or carboxyl groups on and/or near its surface, it is obtained bypolymerizing a silicone hydrogel lens formulation comprising a reactivevinylic monomer.

Examples of preferred reactive vinylic monomers include withoutlimitation amino-C₂-C₆ alkyl (meth)acrylate, C₁-C₆ alkylamino-C₂-C₆alkyl (meth)acrylate, allylamine, vinylamine, amino-C₂-C₆ alkyl(meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl (meth)acrylamide, acrylicacid, C₁-C₁₂ alkylacrylic acid (e.g., methacrylic acid, ethylacrylicacid, propylacrylic acid, butylacrylic acid, pentylacrylic acid, etc.),N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonic acid),alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid,angelic acid, cinnamic acid, 1-carboxy-4-phenyl butadiene-1,3, itaconicacid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid,maleic acid, fumaric acid, tricarboxy ethylene, and combinationsthereof. Preferably, the SiHy contact lens is made from a lensformulation comprising at least one reactive vinylic monomer selectedfrom the group consisting of amino-C₂-C₆ alkyl (meth)acrylate, C₁-C₆alkylamino-C₂-C₆ alkyl (meth)acrylate, allylamine, vinylamine,amino-C₁-C₆ alkyl (meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl(meth)acrylamide, acrylic acid, C₁-C₁₂ alkylacrylic acid,N,N-2-acrylamidoglycolic acid, and combinations thereof.

The lens formulation comprises preferably from about 0.1% to about 10%,more preferably from about 0.25% to about 7%, even more preferably fromabout 0.5% to about 5%, most preferably from about 0.75% to about 3%, byweight of a reactive vinylic monomer described above.

A preformed SiHy contact lens can also be subjected either to a surfacetreatment to form a reactive base coating having amino groups and/orcarboxyl groups on the surface of the contact lens. Examples of surfacetreatments include without limitation a surface treatment by energy(e.g., a plasma, a static electrical charge, irradiation, or otherenergy source), chemical treatments, chemical vapor deposition, thegrafting of hydrophilic vinylic monomers or macromers onto the surfaceof an article, layer-by-layer coating (“LbL coating”) obtained accordingto methods described in U.S. Pat. Nos. 6,451,871, 6,719,929, 6,793,973,6,811,805, and 6,896,926 and in U.S. Patent Application Publication Nos.2007/0229758A1, 2008/0152800A1, and 2008/0226922A1, (herein incorporatedby references in their entireties). “LbL coating”, as used herein,refers to a coating that is not covalently attached to the polymermatrix of a contact lens and is obtained through a layer-by-layer(“LbL”) deposition of charged or chargeable (by protonation ordeprotonation) and/or non-charged materials on the lens. An LbL coatingcan be composed of one or more layers.

Preferably, the surface treatment is an LbL coating process. In thispreferred embodiment (i.e., the reactive LbL base coating embodiment), aresultant silicone hydrogel contact lens comprises a reactive LbL basecoating (i.e., the two transition layers) including at least one layerof a reactive polymer (i.e., a polymer having pendant amino groupsand/or carboxyl groups), wherein the reactive LbL base coating isobtained by contacting the contact lens with a solution of a reactivepolymer. Contacting of a contact lens with a coating solution of areactive polymer can occur by dipping it into the coating solution or byspraying it with the coating solution. One contacting process involvessolely dipping the contact lens in a bath of a coating solution for aperiod of time or alternatively dipping the contact lens sequentially ina series of baths of coating solutions for a fixed shorter time periodfor each bath. Another contacting process involves solely spray acoating solution. However, a number of alternatives involve variouscombinations of spraying- and dipping-steps may be designed by a personhaving ordinary skill in the art. The contacting time of a contact lenswith a coating solution of a reactive polymer may last up to about 10minutes, preferably from about 5 to about 360 seconds, more preferablyfrom about 5 to about 250 seconds, even more preferably from about 5 toabout 200 seconds.

In accordance with this reactive LbL base coating embodiment, thereactive polymer can be a linear or branched polymer having pendantamino groups and/or carboxyl groups. Any polymers having pendant aminogroups and/or carboxyl groups can be used as a reactive polymer forforming base coatings on silicone hydrogel contact lenses. Examples ofsuch reactive polymers include without limitation: a homopolymer of areactive vinylic monomer; a copolymer of two or more reactive vinylicmonomers; a copolymer of a reactive vinylic monomer with one or morenon-reactive hydrophilic vinylic monomers (i.e., hydrophilic vinylicmonomers free of any carboxyl or (primary or secondary) amino group);polyethyleneimine (PEI); polyvinylalcohol with pendant amino groups; acarboxyl-containing cellulose (e.g., carboxymethylcellulose,carboxyethylcellulose, carboxypropylcellulose); hyaluronate; chondroitinsulfate; poly(glutamic acid); poly(aspartic acid); and combinationsthereof.

Any preferred reactive vinylic monomers described above can be used inthis embodiment for forming a reactive polymer for forming a reactiveLbL base coating.

Preferred examples of non-reactive hydrophilic vinylic monomers free ofcarboxyl or amino group include without limitation acrylamide (AAm),methacrylamide N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide(DMMA), N-vinylpyrrolidone (NVP), N,N,-dimethylaminoethylmethacrylate(DMAEM), N,N-dimethylaminoethylacrylate (DMAEA),N,N-dimethylaminopropylmethacrylamide (DMAPMAm),N,N-dimethylaminopropylacrylamide (DMAPAAm), glycerol methacrylate,3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate,C₁-C₄-alkoxy polyethylene glycol (meth)acrylate having a weight averagemolecular weight of up to 1500 Daltons, N-vinyl formamide, N-vinylacetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allylalcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in thecopolymer), a phosphorylcholine-containing vinylic monomer (including(meth)acryloyloxyethyl phosphorylcholine and those described in U.S.Pat. No. 5,461,433, herein incorporated by reference in its entirety),and combinations thereof.

Preferably, the reactive polymers for forming a reactive LbL basecoating are polyacrylic acid, polymethacrylic acid, poly(C₂-C₁₂alkylacrylic acid), poly(acrylic acid-co-methacrylic acid), poly[C₂-C₁₂alkylacrylic acid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolicacid), poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylicacid-co-vinylpyrrolidone], poly[C₂-C₁₂ alkylacrylic acid-co-acrylamide],poly[C₂-C₁₂ alkylacrylic acid-co-vinylpyrrolidone], hydrolyzedpoly[(meth)acrylic acid-co-vinylacetate], hydrolyzed poly[C₂-C₁₂alkylacrylic acid-co-vinylacetate], polyethyleneimine (PEI),polyallylamine hydrochloride (PAH) homo- or copolymer, polyvinylaminehomo- or copolymer, or combinations thereof.

The weight average molecular weight M_(w) of a reactive polymer forforming a reactive LbL base coating is at least about 10,000 Daltons,preferably at least about 50,000 Daltons, more preferably from about100,000 Daltons to 5,000,000 Daltons.

A solution of a reactive polymer for forming a reactive LbL base coatingon contact lenses can be prepared by dissolving one or more reactivepolymers in water, a mixture of water and one or more organic solventsmiscible with water, an organic solvent, or a mixture of one or moreorganic solvent. Preferably, the reactive polymer is dissolved in amixture of water and one or more organic solvents, an organic solvent,or a mixture of one or more organic solvent. It is believed that asolvent system containing at least one organic solvent can swell apreformed SiHy contact lens so that a portion of the reactive polymermay penetrate into the preformed SiHy contact lens and increase thedurability of the reactive base coating. Any organic solvents describedabove can be used in preparation of a solution of the reactive polymer,so long as it can dissolve the reactive polymer.

In another preferred embodiment, a preformed SiHy contact lens comprisesinherently amino groups and/or carboxyl groups on and/or near itssurface and is further subjected to a surface treatment to form areactive LbL base coating having amino groups and/or carboxyl groupstherein.

In another preferred embodiment (reactive plasma base coating), apreformed SiHy contact lens is subjected to a plasma treatment to form acovalently-attached reactive plasma base coating on the contact lens,i.e., polymerizing one or more reactive vinylic monomers (any one ofthose described previously) under the effect of plasma generated byelectric discharge (so-called plasma-induced polymerization). The term“plasma” denotes an ionized gas, e.g. created by electric glow dischargewhich may be composed of electrons, ions of either polarity, gas atomsand molecules in the ground or any higher state of any form ofexcitation, as well as of photons. It is often called “low temperatureplasma”. For a review of plasma polymerization and its uses reference ismade to R. Hartmann “Plasma polymerisation: Grundlagen, Technik andAnwendung, Jahrb. Oberflächentechnik (1993) 49, pp. 283-296,Battelle-Inst. e.V. Frankfurt/Main Germany; H. Yasuda, “Glow DischargePolymerization”, Journal of Polymer Science: Macromolecular Reviews,vol. 16 (1981), pp. 199-293; H. Yasuda, “Plasma Polymerization”,Academic Press, Inc. (1985); Frank Jansen, “Plasma DepositionProcesses”, in “Plasma Deposited Thin Films”, ed. by T. Mort and F.Jansen, CRC Press Boca Raton (19); O. Auciello et al. (ed.)“Plasma-Surface Interactions and Processing of Materials” publ. byKluwer Academic Publishers in NATO ASI Series; Series E: AppliedSciences, vol. 176 (1990), pp. 377-399; and N. Dilsiz and G. Akovali“Plasma Polymerization of Selected Organic Compounds”, Polymer, vol. 37(1996) pp. 333-341. Preferably, the plasma-induced polymerization is an“after-glow” plasma-induced polymerization as described in WO98028026(herein incorporated by reference in its entirety). For “after-glow”plasma polymerization the surface of a contact lens is treated firstwith a non-polymerizable plasma gas (e.g. H2, He or Ar) and then in asubsequent step the surface thus activated is exposed to a vinylicmonomer having an amino group or carboxyl group (any reactive vinylicmonomer described above), while the plasma power having been switchedoff. The activation results in the plasma-induced formation of radicalson the surface which in the subsequent step initiate the polymerizationof the vinylic monomer thereon.

In accordance with the invention, the water-soluble and crosslinkablehydrophilic polymeric material for forming the outer hydrogel layers (orcrosslinked coating) comprises crosslinkable groups, preferablythermally-crosslinkable groups, more preferably azetidinium groups.Preferably, the water-soluble and crosslinkable hydrophilic polymericmaterial for forming the outer hydrogel layers (or crosslinked coating)is a partially-crosslinked polymeric material that comprises athree-dimensional network and crosslinkable (preferablythermally-crosslinkable) groups, more preferably azetidinium groupswithin the network. The term “partially-crosslinked” in reference to apolymeric material means that the crosslinkable groups of startingmaterials for making the polymeric material in crosslinking reactionhave not been fully consumed. Examples of crosslinkable groups includewithout limitation azetidinium groups, epoxy groups, isocyanate groups,aziridine groups, azlactone groups, and combinations thereof.

In a preferred embodiment, the water-soluble and crosslinkablehydrophilic polymeric material for forming the outer hydrogel layers (orcrosslinked coating) comprises (i) from about 20% to about 95% by weightof first polymer chains derived from an epichlorohydrin-functionalizedpolyamine or polyamidoamine, (ii) from about 5% to about 80% by weightof hydrophilic moieties or second polymer chains derived from at leastone hydrophilicity-enhancing agent having at least one reactivefunctional group selected from the group consisting of amino group,carboxyl group, thiol group, and combination thereof, wherein thehydrophilic moieties or second polymer chains are covalently attached tothe first polymer chains through one or more covalent linkages eachformed between one azetitdinium group of theepichlorohydrin-functionalized polyamine or polyamidoamine and oneamino, carboxyl or thiol group of the hydrophilicity-enhancing agent,and (iii) azetidinium groups which are parts of the first polymer chainsor pendant or terminal groups covalently attached to the first polymerchains.

With such a water-soluble and crosslinkable hydrophilic polymericmaterial, the outer hydrogel layers (or crosslinked coating) can beformed by simply heating a preformed SiHy contact lens (having aminoand/or carboxyl groups on and/or near the surface of the contact lens,or a base coating comprising amino and/or carboxyl groups) in an aqueoussolution in the presence of the hydrophilic polymeric material to and ata temperature from about 40° C. to about 140° C. for a period of timesufficient to covalently attach the hydrophilic polymeric material ontothe surface of the contact lens through covalent linkages each formedbetween one azetidinium group of the hydrophilic polymeric material andone of the amino and/or carboxyl groups on and/or near the surface ofthe contact lens, thereby forming a crosslinked hydrophilic coating onthe contact lens. It is understood that any water-soluble andcrosslinkable hydrophilic polymeric material containing crosslinkablegroups (e.g., those described above) can be used in the invention toform the anterior and posterior outer hydrogel layers of a SiHy contactlens.

A water-soluble and thermally-crosslinkable hydrophilic polymericmaterial containing azetidinium groups comprises (i.e., has acomposition including) from about 20% to about 95%, preferably fromabout 35% to about 90%, more preferably from about 50% to about 85%, byweight of first polymer chains derived from anepichlorohydrin-functionalized polyamine or polyamidoamine and fromabout 5% to about 80%, preferably from about 10% to about 65%, even morepreferably from about 15% to about 50%, by weight of hydrophilicmoieties or second polymer chains derived from at least onehydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,thiol group, and combination thereof. The composition of the hydrophilicpolymeric material is determined by the composition (based on the totalweight of the reactants) of a reactants mixture used for preparing thethermally-crosslinkable hydrophilic polymeric material according to thecrosslinking reactions shown in Scheme I above. For example, if areactant mixture comprises about 75% by weight of anepichlorohydrin-functionalized polyamine or polyamidoamine and about 25%by weight of at least one hydrophilicity-enhancing agent based on thetotal weight of the reactants, then the resultant hydrophilic polymericmaterial comprise about 75% by weight of first polymer chains derivedfrom the epichlorohydrin-functionalized polyamine or polyamidoamine andabout 25% by weight of hydrophilic moieties or second polymer chainsderived from said at least one hydrophilicity-enhancing agent. Theazetidinium groups of the thermally-crosslinkable hydrophilic polymericmaterial are those azetidinium groups (of theepichlorohydrin-functionalized polyamine or polyamidoamine) which do notparticipate in crosslinking reactions for preparing thethermally-crosslinkable hydrophilic polymeric material.

An epichlorohydrin-functionalized polyamine or polyamidoamine can beobtained by reacting epichlorohydrin with a polyamine polymer or apolymer containing primary or secondary amino groups. For example, apoly(alkylene imines) or a poly(amidoamine) which is a polycondensatederived from a polyamine and a dicarboxylic acid (e.g., adipicacid-diethylenetriamine copolymers) can react with epichlorohydrin toform an epichlorohydrin-functionalized polymer. Similarly, a homopolymeror copolymer of aminoalkyl(meth)acrylate, mono-alkylaminoalkyl(meth)acrylate, aminoalkyl(meth)acrylamide, or mono-alkylaminoalkyl(meth)acrylamide can also react with epichlorohydrin to form anepichlorohydrin-functionalized polyamine. The reaction conditions forepichlorohydrin-functionalization of a polyamine or polyamidoaminepolymer are taught in EP1465931 (herein incorporated by reference in itsentirety). A preferred epichlorohydrin-functionalized polymer ispolyaminoamide-epichlorohydrin (PAE) (orpolyimide-polyamine-epichlorohydrin or polyamide-epichlorohydrin), suchas, for example, Kymene® or Polycup® resins(epichlorohydrin-functionalized adipic acid-diethylenetriaminecopolymers) from Hercules or Polycup® or Servamine® resins fromServo/Delden.

Any suitable hydrophilicity-enhancing agents can be used in theinvention so long as they contain at least one amino group, at least onecarboxyl group, and/or at least one thiol group.

A preferred class of hydrophilicity-enhancing agents include withoutlimitation: amino-, carboxyl- or thiol-containing monosaccharides (e.g.,3-amino-1,2-propanediol, 1-thiolglycerol, 5-keto-D-gluconic acid,galactosamine, glucosamine, galacturonic acid, gluconic acid,glucosaminic acid, mannosamine, saccharic acid 1,4-lactone, saccharideacid, Ketodeoxynonulosonic acid, N-methyl-D-glucamine,1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol,1-methylamino-1-deoxysorbitol, N-aminoethyl gluconamide); amino-,carboxyl- or thiol-containing disaccharides (e.g., chondroitindisaccharide sodium salt, di(β-D-xylopyranosyl)amine, digalacturonicacid, heparin disaccharide, hyaluronic acid disaccharide, Lactobionicacid); and amino-, carboxyl- or thiol-containing oligosaccharides (e.g.,carboxymethyl-β-cyclodextrin sodium salt, trigalacturonic acid); andcombinations thereof.

Another preferred class of hydrophilicity-enhancing agents ishydrophilic polymers having one or more amino, carboxyl and/or thiolgroups. More preferably, the content of monomeric units having an amino(—NHR′ with R′ as defined above), carboxyl (—COOH) and/or thiol (—SH)group in a hydrophilic polymer as a hydrophilicity-enhancing agent isless than about 40%, preferably less than about 30%, more preferablyless than about 20%, even more preferably less than about 10%, by weightbased on the total weight of the hydrophilic polymer.

One preferred class of hydrophilic polymers as hydrophilicity-enhancingagents are amino- or carboxyl-containing polysaccharides, for example,such as, carboxymethylcellulose (having a carboxyl content of about 40%or less, which is estimated based on the composition of repeating units,—[C₆H_(10-m)O₅(CH₂CO₂H)_(m)]— in which m is 1 to 3),carboxyethylcellulose (having a carboxyl content of about 36% or less,which is estimated based on the composition of repeating units,—[C₆H_(10-m)O₅(C₂H₄CO₂H)_(m)]— in which m is 1 to 3)carboxypropylcellulose (having a carboxyl content of about 32% or less,which is estimated based on the composition of repeating units,—[C₆H_(10-m)O₅(C₃H₆CO₂H)_(m)]—, in which m is 1 to 3), hyaluronic acid(having a carboxyl content of about 11%, which is estimated based on thecomposition of repeating units, —(C₁₃H₂₀O₉NCO₂H)—), chondroitin sulfate(having a carboxyl content of about 9.8%, which is estimated based onthe composition of repeating units, —(O₁₂H₁₈O₁₃NS CO₂H)—), orcombinations thereof.

Another preferred class of hydrophilic polymers ashydrophilicity-enhancing agents include without limitation:poly(ethylene glycol) (PEG) with mono-amino, carboxyl or thiol group(e.g., PEG-NH₂, PEG-SH, PEG-COOH); H₂N-PEG-NH₂; HOOC-PEG-COOH;HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH; H₂N-PEG-SH; multi-arm PEG with oneor more amino, carboxyl or thiol groups; PEG dendrimers with one or moreamino, carboxyl or thiol groups; a diamino- or dicarboxyl-terminatedhomo- or co-polymer of a non-reactive hydrophilic vinylic monomer; amonoamino- or monocarboxyl-terminated homo- or co-polymer of anon-reactive hydrophilic vinylic monomer; a copolymer which is apolymerization product of a composition comprising (1) about 60% byweight or less, preferably from about 0.1% to about 30%, more preferablyfrom about 0.5% to about 20%, even more preferably from about 1% toabout 15%, by weight of one or more reactive vinylic monomers and (2) atleast one non-reactive hydrophilic vinylic monomer and/or at least onephosphorylcholine-containing vinylic monomer; and combinations thereof.Reactive vinylic monomer(s) and non-reactive hydrophilic vinylicmonomer(s) are those described previously.

More preferably, a hydrophilic polymer as a hydrophilicity-enhancingagent is PEG-NH₂; PEG-SH; PEG-COOH; H₂N-PEG-NH₂; HOOC-PEG-COOH;HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH; H₂N-PEG-SH; multi-arm PEG with oneor more amino, carboxyl or thiol groups; PEG dendrimers with one or moreamino, carboxyl or thiol groups; a monoamino-, monocarboxyl-, diamino-or dicarboxyl-terminated homo- or copolymer of a non-reactivehydrophilic vinylic monomer selected from the group consisting ofacrylamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone(NVP), N-vinyl-N-methyl acetamide, glycerol (meth)acrylate, hydroxyethyl(meth)acrylate, N-hydroxyethyl (meth)acrylamide, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 400 Daltons, vinyl alcohol,N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl(meth)acrylate, N,N-dimethylaminopropyl (metha)crylamide,(meth)acryloyloxyethyl phosphorylcholine, and combinations thereof; acopolymer which is a polymerization product of a composition comprising(1) from about 0.1% to about 30%, preferably from about 0.5% to about20%, more preferably from about 1% to about 15%, by weight of(meth)acrylic acid, C₂-C₁₂ alkylacrylic acid, vinylamine, allylamine,and/or amino-C₂-C₄ alkyl (meth)acrylate, and (2) (meth)acryloyloxyethylphosphorylcholine and/or at least one non-reactive hydrophilic vinylicmonomer selected from the group consisting of acrylamide,N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methyl acetamide,glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl(meth)acrylamide, C₁-C₄-alkoxy polyethylene glycol (meth)acrylate havinga weight average molecular weight of up to 400 Daltons, vinyl alcohol,and combination thereof.

Most preferably, the hydrophilicity-enhancing agent as ahydrophilicity-enhancing agent is PEG-NH₂; PEG-SH; PEG-COOH; monoamino-,monocarboxyl-, diamino- or dicarboxyl-terminated polyvinylpyrrolidone;monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpolyacrylamide; monoamino-, monocarboxyl-, diamino- ordicarboxyl-terminated poly(DMA); monoamino- or monocarboxyl-, diamino-or dicarboxyl-terminated poly(DMA-co-NVP); monoamino-, monocarboxyl-,diamino- or dicarboxyl-terminated poly(NVP-co-N,N-dimethylaminoethyl(meth)acrylate)); monoamino-, monocarboxyl-, diamino- ordicarboxyl-terminated poly(vinylalcohol); monoamino-, monocarboxyl-,diamino- or dicarboxyl-terminated poly[(meth)acryloyloxyethylphosphrylcholine] homopolymer or copolymer; monoamino-, monocarboxyl-,diamino- or dicarboxyl-terminated poly(NVP-co-vinyl alcohol);monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpoly(DMA-co-vinyl alcohol); poly[(meth)acrylic acid-co-acrylamide] withfrom about 0.1% to about 30%, preferably from about 0.5% to about 20%,more preferably from about 1% to about 15%, by weight of (meth)acrylicacid; poly[(meth)acrylic acid-co-NVP) with from about 0.1% to about 30%,preferably from about 0.5% to about 20%, more preferably from about 1%to about 15%, by weight of (meth)acrylic acid; a copolymer which is apolymerization product of a composition comprising (1)(meth)acryloyloxyethyl phosphorylcholine and (2) from about 0.1% toabout 30%, preferably from about 0.5% to about 20%, more preferably fromabout 1% to about 15%, by weight of a carboxylic acid containing vinylicmonomer and/or an amino-containing vinylic monomer, and combinationthereof.

PEGs with functional groups and multi-arm PEGs with functional groupscan be obtained from various commercial suppliers, e.g., Polyscience,and Shearwater Polymers, inc., etc.

Monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- orcopolymers of one or more non-reactive hydrophilic vinylic monomers orof a phosphorylcholine-containing vinylic monomer can be preparedaccording to procedures described in U.S. Pat. No. 6,218,508, hereinincorporated by reference in its entirety. For example, to prepare adiamino- or dicarboxyl-terminated homo- or co-polymer of a non-reactivehydrophilic vinylic monomer, the non-reactive vinylic monomer, a chaintransfer agent with an amino or carboxyl group (e.g.,2-aminoethanethiol, 2-mercaptopropinic acid, thioglycolic acid,thiolactic acid, or other hydroxymercaptanes, aminomercaptans, orcarboxyl-containing mercaptanes) and optionally other vinylic monomerare copolymerized (thermally or actinically) with a reactive vinylicmonomer (having an amino or carboxyl group), in the presence of anfree-radical initiator. Generally, the molar ratio of chain transferagent to that of all of vinylic monomers other than the reactive vinylicmonomer is from about 1:5 to about 1:100, whereas the molar ratio ofchain transfer agent to the reactive vinylic monomer is 1:1. In suchpreparation, the chain transfer agent with amino or carboxyl group isused to control the molecular weight of the resultant hydrophilicpolymer and forms a terminal end of the resultant hydrophilic polymer soas to provide the resultant hydrophilic polymer with one terminal aminoor carboxyl group, while the reactive vinylic monomer provides the otherterminal carboxyl or amino group to the resultant hydrophilic polymer.Similarly, to prepare a monoamino- or monocarboxyl-terminated homo- orco-polymer of a non-reactive hydrophilic vinylic monomer, thenon-reactive vinylic monomer, a chain transfer agent with an amino orcarboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropinic acid,thioglycolic acid, thiolactic acid, or other hydroxymercaptanes,aminomercaptans, or carboxyl-containing mercaptanes) and optionallyother vinylic monomers are copolymerized (thermally or actinically) inthe absence of any reactive vinylic monomer.

As used in this application, a copolymer of a non-reactive hydrophilicvinylic monomer refers to a polymerization product of a non-reactivehydrophilic vinylic monomer with one or more additional vinylicmonomers. Copolymers comprising a non-reactive hydrophilic vinylicmonomer and a reactive vinylic monomer (e.g., a carboxyl-containingvinylic monomer) can be prepared according to any well-known radicalpolymerization methods or obtained from commercial suppliers. Copolymerscontaining methacryloyloxyethyl phosphorylcholine andcarboxyl-containing vinylic monomer can be obtained from NOP Corporation(e.g., LIPIDURE®-A and -AF).

The weight average molecular weight M_(w) of the hydrophilic polymerhaving at least one amino, carboxyl or thiol group (as ahydrophilicity-enhancing agent) is preferably from about 500 to about1,000,000, more preferably from about 1,000 to about 500,000.

In accordance with the invention, the reaction between ahydrophilicity-enhancing agent and an epichlorohydrin-functionalizedpolyamine or polyamidoamine is carried out at a temperature of fromabout 40° C. to about 100° C. for a period of time sufficient (fromabout 0.3 hour to about 24 hours, preferably from about 1 hour to about12 hours, even more preferably from about 2 hours to about 8 hours) toform a water-soluble and thermally-crosslinkable hydrophilic polymericmaterial containing azetidinium groups.

In accordance with the invention, the concentration of ahydrophilicity-enhancing agent relative to anepichlorohydrin-functionalized polyamine or polyamidoamine must beselected not to render a resultant hydrophilic polymeric materialwater-insoluble (i.e., a solubility of less than 0.005 g per 100 ml ofwater at room temperature) and not to consume more than about 99%,preferably about 98%, more preferably about 97%, even more preferablyabout 96% of the azetidinium groups of theepichlorohydrin-functionalized polyamine or polyamidoamine.

In accordance with the invention, heating is performed preferably byautoclaving a preformed SiHy contact lens that comprises amino and/orcarboxyl groups on and/or near the surface of the contact lens, or abase coating comprising amino and/or carboxyl groups and is immersed ina packaging solution (i.e., a buffered aqueous solution) including awater-soluble thermally crosslinkable hydrophilic polymeric material ina sealed lens package at a temperature of from about 118° C. to about125° C. for approximately 20-90 minutes. In accordance with thisembodiment of the invention, the packaging solution is a bufferedaqueous solution which is ophthalmically safe after autoclave.Alternatively, is performed preferably by autoclaving a preformed SiHycontact lens, which comprises a base coating and a layer of awater-soluble thermally crosslinkabe hydrophilic polymeric material ontop of the base coating, immersed in a packaging solution (i.e., abuffered aqueous solution) in a sealed lens package at a temperature offrom about 118° C. to about 125° C. for approximately 20-90 minutes.

Lens packages (or containers) are well known to a person skilled in theart for autoclaving and storing a soft contact lens. Any lens packagescan be used in the invention. Preferably, a lens package is a blisterpackage which comprises a base and a cover, wherein the cover isdetachably sealed to the base, wherein the base includes a cavity forreceiving a sterile packaging solution and the contact lens.

Lenses are packaged in individual packages, sealed, and sterilized(e.g., by autoclave at about 120° C. or higher for at least 30 minutes)prior to dispensing to users. A person skilled in the art willunderstand well how to seal and sterilize lens packages.

In accordance with the invention, a packaging solution contains at leastone buffering agent and one or more other ingredients known to a personskilled in the art. Examples of other ingredients include withoutlimitation, tonicity agents, surfactants, antibacterial agents,preservatives, and lubricants (or water-soluble viscosity builders)(e.g., cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone).

The packaging solution contains a buffering agent in an amountsufficient to maintain a pH of the packaging solution in the desiredrange, for example, preferably in a physiologically acceptable range ofabout 6 to about 8.5. Any known, physiologically compatible bufferingagents can be used. Suitable buffering agents as a constituent of thecontact lens care composition according to the invention are known tothe person skilled in the art. Examples are boric acid, borates, e.g.sodium borate, citric acid, citrates, e.g. potassium citrate,bicarbonates, e.g. sodium bicarbonate, TRIS(2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris(Bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane),bis-aminopolyols, triethanolamine, ACES(N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES(N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES(2-(N-morpholino)ethanesulfonic acid), MOPS(3-[N-morpholino]-propanesulfonic acid), PIPES(piperazine-N,N′-bis(2-ethanesulfonic acid), TES(N-[Tris(hydroxymethyl)methyl]-2-am inoethanesulfonic acid), saltsthereof, phosphate buffers, e.g. Na₂HPO₄, NaH₂PO₄, and KH₂PO₄ ormixtures thereof. A preferred bis-aminopolyol is1,3-bis(tris[hydroxymethyl]-methylamino)propane (bis-TRIS-propane). Theamount of each buffer agent in a packaging solution is preferably from0.001% to 2%, preferably from 0.01% to 1%; most preferably from about0.05% to about 0.30% by weight.

The packaging solution has a tonicity of from about 200 to about 450milliosmol (mOsm), preferably from about 250 to about 350 mOsm. Thetonicity of a packaging solution can be adjusted by adding organic orinorganic substances which affect the tonicity. Suitable ocularlyacceptable tonicity agents include, but are not limited to sodiumchloride, potassium chloride, glycerol, propylene glycol, polyols,mannitols, sorbitol, xylitol and mixtures thereof.

A packaging solution of the invention has a viscosity of from about 1centipoise to about 20 centipoises, preferably from about 1.2centipoises to about 10 centipoises, more preferably from about 1.5centipoises to about 5 centipoises, at 25° C.

In a preferred embodiment, the packaging solution comprises preferablyfrom about 0.01% to about 2%, more preferably from about 0.05% to about1.5%, even more preferably from about 0.1% to about 1%, most preferablyfrom about 0.2% to about 0.5%, by weight of a water-soluble andthermally-crosslinkable hydrophilic polymeric material of the invention.

A packaging solution of the invention can contain a viscosity-enhancingpolymer. The viscosity-enhancing polymer preferably is nonionic.Increasing the solution viscosity provides a film on the lens which mayfacilitate comfortable wearing of the contact lens. Theviscosity-enhancing component may also act to cushion the impact on theeye surface during insertion and serves also to alleviate eyeirritation.

Preferred viscosity-enhancing polymers include, but are not limited to,water soluble cellulose ethers (e.g., methyl cellulose (MC), ethylcellulose, hydroxymethylcellulose, hydroxyethyl cellulose (HEC),hydroxypropylcellulose (HPC), hydroxypropylmethyl cellulose (HPMC), or amixture thereof), water-soluble polyvinylalcohols (PVAs), high molecularweight poly(ethylene oxide) having a molecular weight greater than about2000 (up to 10,000,000 Daltons), polyvinylpyrrolidone with a molecularweight of from about 30,000 daltons to about 1,000,000 daltons, acopolymer of N-vinylpyrrolidone and at least one dialkylaminoalkyl(meth)acrylate having 7-20 carbon atoms, and combinations thereof. Watersoluble cellulose ethers and copolymers of vinylpyrrolidone anddimethylaminoethylmethacrylate are most preferred viscosity-enhancingpolymers. Copolymers of N-vinylpyrrolidone anddimethylaminoethylmethacrylate are commercially available, e.g.,Copolymer 845 and Copolymer 937 from ISP.

The viscosity-enhancing polymer is present in the packaging solution inan amount of from about 0.01% to about 5% by weight, preferably fromabout 0.05% to about 3% by weight, even more preferably from about 0.1%to about 1% by weight, based on the total amount of the packagingsolution.

A packaging solution can further comprises a polyethylene glycol havinga molecular weight of about 1200 or less, more preferably 600 or less,most preferably from about 100 to about 500 Daltons.

Where at least one of the crosslinked coating and the packaging solutioncontains a polymeric material having polyethylene glycol segments, thepackaging solution preferably comprises an α-oxo-multi-acid or saltthereof in an amount sufficient to have a reduced susceptibility tooxidation degradation of the polyethylene glycol segments. Acommonly-owned co-pending patent application (US patent applicationpublication No. 2004/0116564 A1, incorporated herein in its entirety)discloses that oxo-multi-acid or salt thereof can reduce thesusceptibility to oxidative degradation of a PEG-containing polymericmaterial.

Exemplary α-oxo-multi-acids or biocompatible salts thereof includewithout limitation citric acid, 2-ketoglutaric acid, or malic acid orbiocompatible (preferably ophthalmically compatible) salts thereof. Morepreferably, a α-oxo-multi-acid is citric or malic acid or biocompatible(preferably ophthalmically compatible) salts thereof (e.g., sodium,potassium, or the like).

In accordance with the invention, the packaging solution can furthercomprises mucin-like materials, ophthalmically beneficial materials,and/or surfactants. Exemplary mucin-like materials described above,exemplary ophthalmically beneficial materials described above, exemplarysurfactants described above can be used in this embodiment.

In a preferred embodiment, a SiHy contact lens of the invention has arelatively long water break up time (WBUT). WBUT is the time needed forthe water film to break (de-wet) exposing the underlying lens materialunder visual examination. A SiHy contact lens having a longer WBUT canhold water (tears) film on its surface for a relatively longer periodtime when worn on the eye. It would be less likely to develop dry spotsbetween blinks of the eyelids and could provide enhanced wearingcomfort. WBUT can be measured according to the procedures described inExample hereinafter. Preferably, a SiHy contact lens of the inventionhas a surface hydrophilicity characterized by having a water breakuptime of at least about 10 seconds.

In a preferred embodiment, a SiHy contact lens of the invention has asurface wettability characterized by having an averaged water contactangle of about 90 degrees or less, preferably about 80 degrees or less,more preferably about 70 degrees or less, even more preferably about 60degrees or less, most preferably about 50 degrees or less.

In a preferred embodiment, a SiHy contact lens has an oxygentransmissibility of at least about 40, preferably at least about 60,more preferably at least about 80, even more preferably at least about100, most preferably at least about 120, barrers/mm.

It should be understood that although in this aspect of the inventionvarious embodiments including preferred embodiments of the invention maybe separately described above, they can be combined and/or used togetherin any desirable fashion to arrive at different embodiments of asilicone hydrogel contact lenses of the invention.

In another aspect, the invention provides a hydrated silicone hydrogelcontact lens. A hydrated silicone hydrogel contact lens of the inventioncomprises: a silicone hydrogel material as bulk material, an anteriorsurface and an opposite posterior surface; wherein the contact lens hasan oxygen transmissibility of at least about 40, preferably at leastabout 60, more preferably at least about 80, even more preferably atleast about 110 barrers/mm, and a cross-sectional surface-modulusprofile which comprises, along a shortest line between the anterior andposterior surfaces on the surface of a cross section of the contactlens, an anterior outer zone including and near the anterior surface, aninner zone including and around the center of the shortest line, and aposterior outer zone including and near the posterior surface, whereinthe anterior outer zone has an average anterior surface modulus(designated as SM_(Ant) ) while the posterior outer zone has an averageposterior surface modulus (designated as SM_(Post) ), wherein the innerzone has an average inner surface modulus (designated as SM_(Inner) ),wherein at least one of

$\frac{\overset{\_}{{SM}_{Inner}} - \overset{\_}{{SM}_{Post}}}{\overset{\_}{{SM}_{Inner}}} \times 100\%\mspace{14mu}{and}\mspace{14mu}\frac{\overset{\_}{{SM}_{Inner}} - \overset{\_}{{SM}_{Ant}}}{\overset{\_}{{SM}_{Inner}}} \times 100\%$is at least about 20%, preferably at least about 25%, more preferably atleast about 30%, even more preferably at least about 35%, mostpreferably at least about 40%. Preferably, the anterior and posteriorouter zones covers a span of at least about 0.1 μm, preferably fromabout 0.1 μm to about 20 μm, more preferably from about 0.25 μm to about15 μm, even more preferably from about 0.5 μm to about 12.5 μm, mostpreferably from about 1 μm to about 10 μm.

In a preferred embodiment, the hydrated silicone hydrogel contact lenscan have an elastic modulus (or Young's Modulus) of from about 0.3 MPato about 1.8 MPa, preferably from about 0.4 MPa to about 1.5 MPa, morepreferably from about 0.5 MPa to about 1.2 MPa; a water content of fromabout 10% to about 75%, preferably from about 10% to about 70%, morepreferably from about 15% to about 65%; even more preferably from about20% to about 60%, most preferably from about 25% to about 55% by weight;a surface wettability characterized by having an averaged water contactangle of about 90 degrees or less, preferably about 80 degrees or less,more preferably about 70 degrees or less, even more preferably about 60degrees or less, most preferably about 50 degrees or less; a surfacehydrophilicity characterized by having a WBUT of at least about 10seconds; or combinations thereof.

In another preferred embodiment, the anterior and posterior surfaceshave a low surface concentration of negatively-charged groups (e.g.,carboxylic acid groups) as characterized by attracting at most about200, preferably at most about 160, more preferably at most about 120,even more preferably at most about 90, most preferably at most about 60positively-charged particles in positively-charged-particles-adhesiontest. To have a low surface concentration of negatively charged groups(e.g., carboxylic acid groups), the anterior and posterior outerhydrogel layers should have a relatively low carboxylic acid content.Preferably the anterior and posterior outer hydrogel layers have acarboxylic acid content of about 20% by weight or less, preferably about15% by weight or less, even more preferably about 10% by weight or less,most preferably about 5% by weight or less.

In another preferred embodiment, a SiHy contact lens of the inventionhas a good surface lubricity characterized by having a criticalcoefficient of friction (designated as CCOF) of about 0.046 or less,preferably about 0.043 or less, more preferably about 0.040 or less.Alternatively, a SiHy contact lens of the invention preferably has alubricity better than ACUVUE OASYS or ACUVUE TruEye as measured in ablind test according to the lubricity evaluation procedures described inExample 1.

In another preferred embodiment, the hydrated SiHy contact lenspreferably has a high digital-rubbing resistance as characterized byhaving no surface cracking lines visible under dark field after the SiHycontact lens is rubbed between fingers. It is believed thatdigital-rubbing-induced surface cracking may reduce the surfacelubricity and/or may not be able prevent silicone from migrating ontothe surface (exposure).

In another preferred embodiment, a hydrated SiHy contact lens of theinvention comprises an inner layer of the silicone hydrogel material, ananterior outer hydrogel layer, and a posterior outer hydrogel layer,wherein the anterior and posterior outer hydrogel layers aresubstantially uniform in thickness and merge at the peripheral edge ofthe contact lens to completely enclose the inner layer of the siliconehydrogel material. It is understood that the first and second outerzones in the cross-sectional surface modulus profile correspond to thetwo outer hydrogel layers while the inner zone corresponds to the innerlayer of the silicone hydrogel material. All of the various embodimentsof the outer hydrogel layers (crosslinked coating) as described abovefor the other aspect of the invention can be used, alone or in anycombination, in this aspect of the invention as the outer hydrogellayers. All of the various embodiments of the inner layer of a siliconehydrogel material as described above for the other aspect of theinvention can be used, alone or in any combination, in this aspect ofthe invention as the inner layer of the silicone hydrogel material.

In accordance with this aspect of the invention, the outer hydrogellayers are substantially uniform in thickness and have a thickness of atleast about 0.1 μm, preferably from about 0.1 μm to about 20 μm, morepreferably from about 0.25 μm to about 15 μm, even more preferably fromabout 0.5 μm to about 12.5 μm, most preferably from about 1 μm to about10 μm. The thickness of each outer hydrogel layer of a SiHy contact lensof the invention is determined by AFM analysis of a cross section of theSiHy contact lens in fully hydrated state as described above. In a morepreferred embodiment, the thickness of each outer hydrogel layer is atmost about 30% (i.e., 30% or less), preferably at most about 20% (20% orless), more preferably at most about 10% (10% or less) of the centerthickness of the SiHy contact lens in fully hydrated state. In addition,each of the two outer hydrogel layers is substantially free of silicone(as characterized by having a silicon atomic percentage of about 5% orless, preferably about 4% or less, even more preferably about 3% orless, of total elemental percentage, as measured by XPS analysis of thecontact lens in dried state), preferably totally free of silicone. It isunderstood that a small percentage of silicone may be optionally (butpreferably not) incorporated into the polymer network of the outerhydrogel layer so long as it would not significantly deteriorate thesurface properties (hydrophilicity, wettability, and/or lubricity) of aSiHy contact lens.

In another preferred embodiment, the two outer hydrogel layers of ahydrated SiHy contact lens of the invention comprise a water contenthigher than the water content (designated WC_(Lens)) of the hydratedsilicone hydrogel contact lens and more specifically must be at leastabout 1.2 folds (i.e., 120%) of WC_(Lens). It is believed that thewater-swelling ratio of each outer hydrogel layer can representapproximately the water content of the outer hydrogel layer as discussedabove. Where WC_(Lens) is about 45% or less, the water-swelling ratio ofeach outer hydrogel layer is preferably at least at least about 150%,more preferably at least about 200%, more preferably at least about250%, even more preferably at least about 300%. Where WC_(Lens) ishigher than 45%, the water-swelling ratio of each outer hydrogel layeris at least about

${\frac{120 \cdot {WC}_{Lens}}{1 - {WC}_{Lens}}\%}\mspace{14mu},$preferably about

${\frac{130 \cdot {WC}_{Lens}}{1 - {WC}_{Lens}}\%}\mspace{14mu},$more preferably about

${\frac{140 \cdot {WC}_{Lens}}{1 - {WC}_{Lens}}\%}\mspace{14mu},$even more preferably about

$\frac{150 \cdot {WC}_{Lens}}{1 - {WC}_{Lens}}{\%\mspace{14mu}.}$In alternatively preferred embodiments, where WC_(Lens) is about 55% orless, the water-swelling ratio of each outer hydrogel layer is at leastabout 150%; where WC_(Lens) is about 60% or less, the water-swellingratio of each outer hydrogel layer is at least about 200%; whereWC_(Lens) is about 65% or less, the water-swelling ratio of each outerhydrogel layer is at least about 250%; where WC_(Lens) WC_(Lens) isabout 70% or less, the water-swelling ratio of each outer hydrogel layeris at least about 300%.

Preferably, the SiHy contact lens further comprises a transition layerlocated between the silicone hydrogel material and the outer hydrogellayer. All of the various embodiments of the transition layer asdescribed for the previous aspect of the invention can be used, alone orin any combination, in this aspect of the invention.

A hydrated SiHy contact lens of the invention can be prepared accordingto the methods described above. All of the various embodiments of theinner layer (i.e., silicone hydrogel material) described above can beused, alone or in any combination, in this aspect of the invention asthe silicone hydrogel core. All of the various embodiments as describedabove for the previous aspect of the invention can be used, alone or inany combination, in this aspect of the invention.

It should be understood that although in this aspect of the inventionvarious embodiments including preferred embodiments of the invention maybe separately described above, they can be combined and/or used togetherin any desirable fashion to arrive at different embodiments of asilicone hydrogel contact lenses of the invention. All of the variousembodiments described above for the previous aspect of the invention canbe used alone or in combination in any desirable fashion in this aspectof the invention.

In a further aspect, the invention provides a hydrated silicone hydrogelcontact lens. A hydrated silicone hydrogel contact lens of the inventioncomprises: a silicone hydrogel material as bulk material, an anteriorsurface and an opposite posterior surface; wherein the contact lens has(1) an oxygen transmissibility of at least about 40, preferably at leastabout 60, more preferably at least about 80, even more preferably atleast about 110 barrers/mm, and (2) a surface lubricity characterized byhaving a critical coefficient of friction (designated as CCOF) of about0.046 or less, preferably about 0.043 or less, more preferably about0.040 or less, wherein the anterior and posterior surfaces have a lowsurface concentration of negatively-charged groups including carboxylicacid groups as characterized by attracting at most about 200, preferablyat most about 160, more preferably at most about 120, even morepreferably at most about 90, most preferably at most about 60positively-charged particles in positively-charged-particles-adhesiontest.

In a preferred embodiment, the hydrated silicone hydrogel contact lenshas an elastic modulus (or Young's Modulus) of from about 0.3 MPa toabout 1.8 MPa, preferably from about 0.4 MPa to about 1.5 MPa, morepreferably from about 0.5 MPa to about 1.2 MPa; a water content of fromabout 10% to about 75%, preferably from about 10% to about 70%, morepreferably from about 15% to about 65%; even more preferably from about20% to about 60%, most preferably from about 25% to about 55% by weight;a surface wettability characterized by having an averaged water contactangle of about 90 degrees or less, preferably about 80 degrees or less,more preferably about 70 degrees or less, even more preferably about 60degrees or less, most preferably about 50 degrees or less; a surfacehydrophilicity characterized by having a WBUT of at least about 10seconds; or combinations thereof.

In another preferred embodiment, the hydrated SiHy contact lenspreferably has a high digital-rubbing resistance as characterized byhaving no surface cracking lines visible under dark field after the SiHycontact lens is rubbed between fingers. It is believed thatdigital-rubbing-induced surface cracking may reduce the surfacelubricity and/or may not be able prevent silicone from migrating ontothe surface (exposure).

In another preferred embodiment, a hydrated SiHy contact lens of theinvention comprises an inner layer of the silicone hydrogel material, ananterior outer hydrogel layer, and a posterior outer hydrogel layer,wherein the anterior and posterior outer hydrogel layers aresubstantially uniform in thickness and merge at the peripheral edge ofthe contact lens to completely enclose the inner layer of the siliconehydrogel material. It is understood that the first and second outerzones in the cross-sectional surface modulus profile correspond to thetwo outer hydrogel layers while the inner zone corresponds to the innerlayer of the silicone hydrogel material. All of the various embodimentsof the outer hydrogel layers (crosslinked coating) as described abovefor the other aspect of the invention can be used, alone or in anycombination, in this aspect of the invention as the outer hydrogellayers. All of the various embodiments of the inner layer of a siliconehydrogel material as described above for the other aspect of theinvention can be used, alone or in any combination, in this aspect ofthe invention as the inner layer of the silicone hydrogel material.

In accordance with this aspect of the invention, the outer hydrogellayers are substantially uniform in thickness and have a thickness of atleast about 0.1 μm, preferably from about 0.1 μm to about 20 μm, morepreferably from about 0.25 μm to about 15 μm, even more preferably fromabout 0.5 μm to about 12.5 μm, most preferably from about 1 μm to about10 μm. The thickness of each outer hydrogel layer of a SiHy contact lensof the invention is determined by AFM analysis of a cross section of theSiHy contact lens in fully hydrated state as described above. In a morepreferred embodiment, the thickness of each outer hydrogel layer ispreferably at most about 30% (i.e., 30% or less), preferably at mostabout 20% (20% or less), more preferably at most about 10% (10% or less)of the center thickness of the SiHy contact lens in fully hydratedstate. In addition, each of the two outer hydrogel layers issubstantially free of silicone (as characterized by having a siliconatomic percentage of about 5% or less, preferably about 4% or less, evenmore preferably about 3% or less, of total elemental percentage, asmeasured by XPS analysis of the contact lens in dried state), preferablytotally free of silicone. It is understood that a small percentage ofsilicone may be optionally (but preferably not) incorporated into thepolymer network of the outer hydrogel layer so long as it would notsignificantly deteriorate the surface properties (hydrophilicity,wettability, and/or lubricity) of a SiHy contact lens. To have a lowsurface concentration of negatively charged groups (e.g., carboxylicacid groups), the anterior and posterior outer hydrogel layers shouldhave a relatively low carboxylic acid content. Preferably the anteriorand posterior outer hydrogel layers have a carboxylic acid content ofabout 20% by weight or less, preferably about 15% by weight or less,even more preferably about 10% by weight or less, most preferably about5% by weight or less.

In another preferred embodiment, the two outer hydrogel layers of ahydrated SiHy contact lens of the invention comprise a water contenthigher than the water content (designated WC_(Lens)) of the hydratedsilicone hydrogel contact lens and more specifically must be at leastabout 1.2 folds (i.e., 120%) of the water content (WC_(Lens)) of thehydrated silicone hydrogel contact lens. It is believed that thewater-swelling ratio of each outer hydrogel layer can representapproximately the water content of the outer hydrogel layer as discussedabove. Where WC_(Lens) is about 45% or less, the water-swelling ratio ofeach outer hydrogel layer is preferably at least at least about 150%,more preferably at least about 200%, more preferably at least about250%, even more preferably at least about 300%. Where WC_(Lens) ishigher than 45%, the water-swelling ratio of each outer hydrogel layeris at least about

${\frac{120 \cdot {WC}_{Lens}}{1 - {WC}_{Lens}}\%}\mspace{14mu},$preferably about

${\frac{130 \cdot {WC}_{Lens}}{1 - {WC}_{Lens}}\%}\mspace{14mu},$more preferably about

${\frac{140 \cdot {WC}_{Lens}}{1 - {WC}_{Lens}}\%}\mspace{14mu},$even more preferably about

$\frac{150 \cdot {WC}_{Lens}}{1 - {WC}_{Lens}}{\%\mspace{14mu}.}$In alternatively preferred embodiments, where WC_(Lens) is about 55% orless, the water-swelling ratio of each outer hydrogel layer is at leastabout 150%; where WC_(Lens) is about 60% or less, the water-swellingratio of each outer hydrogel layer is at least about 200%; whereWC_(Lens) is about 65% or less, the water-swelling ratio of each outerhydrogel layer is at least about 250%; where WC_(Lens) is about 70% orless, the water-swelling ratio of each outer hydrogel layer is at leastabout 300%.

In another preferred embodiment, the anterior and posterior outerhydrogel layers independent of each other have a reduced surface modulusof at least about 20%, preferably at least about 25%, more preferably atleast about 30%, even more preferably at least about 35%, mostpreferably at least about 40%, relative to the inner layer.

Preferably, the SiHy contact lens further comprises a transition layerlocated between the silicone hydrogel material and the outer hydrogellayer. All of the various embodiments of the transition layer asdescribed for the previous aspect of the invention can be used, alone orin any combination, in this aspect of the invention.

A hydrated SiHy contact lens of the invention can be prepared accordingto the methods described above. All of the various embodiments of theinner layer (i.e., silicone hydrogel material) described above can beused, alone or in any combination, in this aspect of the invention asthe silicone hydrogel core. All of the various embodiments as describedabove for the previous aspect of the invention can be used, alone or inany combination, in this aspect of the invention.

It should be understood that although in this aspect of the inventionvarious embodiments including preferred embodiments of the invention maybe separately described above, they can be combined and/or used togetherin any desirable fashion to arrive at different embodiments of asilicone hydrogel contact lenses of the invention. All of the variousembodiments described above for the previous aspect of the invention canbe used alone or in combination in any desirable fashion in this aspectof the invention.

The previous disclosure will enable one having ordinary skill in the artto practice the invention. Various modifications, variations, andcombinations can be made to the various embodiment described herein. Inorder to better enable the reader to understand specific embodiments andthe advantages thereof, reference to the following examples issuggested. It is intended that the specification and examples beconsidered as exemplary.

Although various aspects and various embodiments of the invention havebeen described using specific terms, devices, and methods, suchdescription is for illustrative purposes only. The words used are wordsof description rather than of limitation. It is to be understood thatchanges and variations may be made by those skilled in the art withoutdeparting from the spirit or scope of the present invention, which isset forth in the following claims. In addition, it should be understoodthat aspects of the various embodiments may be interchanged either inwhole or in part or can be combined in any manner and/or used together.Therefore, the spirit and scope of the appended claims should not belimited to the description of the preferred versions contained therein.

Example 1

Oxygen Permeability Measurements

The apparent oxygen permeability of a lens and oxygen transmissibilityof a lens material is determined according to a technique similar to theone described in U.S. Pat. No. 5,760,100 and in an article by Wintertonet al., (The Cornea: Transactions of the World Congress on the Cornea111, H. D. Cavanagh Ed., Raven Press: New York 1988, pp 273-280), bothof which are herein incorporated by reference in their entireties.Oxygen fluxes (J) are measured at 34° C. in a wet cell (i.e., gasstreams are maintained at about 100% relative humidity) using a Dk1000instrument (available from Applied Design and Development Co., Norcross,Ga.), or similar analytical instrument. An air stream, having a knownpercentage of oxygen (e.g., 21%), is passed across one side of the lensat a rate of about 10 to 20 cm³/min., while a nitrogen stream is passedon the opposite side of the lens at a rate of about 10 to 20 cm³/min. Asample is equilibrated in a test media (i.e., saline or distilled water)at the prescribed test temperature for at least 30 minutes prior tomeasurement but not more than 45 minutes. Any test media used as theoverlayer is equilibrated at the prescribed test temperature for atleast 30 minutes prior to measurement but not more than 45 minutes. Thestir motor's speed is set to 1200±50 rpm, corresponding to an indicatedsetting of 400±15 on the stepper motor controller. The barometricpressure surrounding the system, P_(measured), is measured. Thethickness (t) of the lens in the area being exposed for testing isdetermined by measuring about 10 locations with a Mitotoya micrometerVL-50, or similar instrument, and averaging the measurements. The oxygenconcentration in the nitrogen stream (i.e., oxygen which diffusesthrough the lens) is measured using the DK1000 instrument. The apparentoxygen permeability of the lens material, Dk_(app), is determined fromthe following formula:Dk _(app) ⁼ Jt/(P _(oxygen))where J=oxygen flux [microliters O₂/cm²-minute]

P_(oxygen)=(P_(measured)−P_(water) vapor)=(% O₂ in air stream) [mmHg]=partial pressure of oxygen in the air stream

P_(measured)=barometric pressure (mm Hg)

P_(water) vapor=0 mm Hg at 34° C. (in a dry cell) (mm Hg)

P_(water) vapor=40 mm Hg at 34° C. (in a wet cell) (mm Hg)

t=average thickness of the lens over the exposed test area (mm)

Dk_(app) is expressed in units of barrers.

The apparent oxygen transmissibility (Dk/t) of the material may becalculated by dividing the apparent oxygen permeability (Dk_(app)) bythe average thickness (t) of the lens.

The above described measurements are not corrected for the so-calledboundary layer effect which is attributable to the use of a water orsaline bath on top of the contact lens during the oxygen fluxmeasurement. The boundary layer effect causes the reported value for theapparent Dk of a silicone hydrogel material to be lower than the actualintrinsic Dk value. Further, the relative impact of the boundary layereffect is greater for thinner lenses than with thicker lenses. The neteffect is that the reported Dk appear to change as a function of lensthickness when it should remain constant.

The intrinsic Dk value of a lens can be estimated based on a Dk valuecorrected for the surface resistance to oxygen flux caused by theboundary layer effect as follows.

Measure the apparent oxygen permeability values (single point) of thereference lotrafilcon A (Focus® N&D® from CIBA VISION CORPORATION) orlotrafilcon B (AirOptix™ from CIBA VISION CORPORATION) lenses using thesame equipment. The reference lenses are of similar optical power as thetest lenses and are measured concurrently with the test lenses.

Measure the oxygen flux through a thickness series of lotrafilcon A orlotrafilcon B (reference) lenses using the same equipment according tothe procedure for apparent Dk measurements described above, to obtainthe intrinsic Dk value (Dk_(i)) of the reference lens. A thicknessseries should cover a thickness range of approximately 100 μm or more.Preferably, the range of reference lens thicknesses will bracket thetest lens thicknesses. The Dk_(app) of these reference lenses must bemeasured on the same equipment as the test lenses and should ideally bemeasured contemporaneously with the test lenses. The equipment setup andmeasurement parameters should be held constant throughout theexperiment. The individual samples may be measured multiple times ifdesired.

Determine the residual oxygen resistance value, R₁, from the referencelens results using equation 1 in the calculations.

$\begin{matrix}{R_{r} = \frac{\Sigma\left( {\frac{t}{{Dk}_{app}} - \frac{t}{{Dk}_{i}}} \right)}{n}} & (1)\end{matrix}$in which t is the thickness of the test lens (i.e., the reference lenstoo), and n is the number of the reference lenses measured. Plot theresidual oxygen resistance value, R_(r) vs. t data and fit a curve ofthe form Y=a+bX where, for the jth lens, Y_(j)=(ΔP/J)_(j) and X=t_(j).The residual oxygen resistance, R_(r) is equal to a.

Use the residual oxygen resistance value determined above to calculatethe correct oxygen permeability Dk_(c) (estimated intrinsic Dk) for thetest lenses based on Equation 2.Dk _(c) =t/[(t/Dk _(a))−R _(r)]  (2)

The estimated intrinsic Dk of the test lens can be used to calculatewhat the apparent Dk (Dk_(a_std)) would have been for a standardthickness lens in the same test environment based on Equation 3. Thestandard thickness (t_(std)) for lotrafilcon A=85 μm. The standardthickness for lotrafilcon B=60 μm.Dk _(a_std) =t _(std)/[(t _(std) /Dk _(c))+R _(r_std)]  (3)Ion Permeability Measurements.

The ion permeability of a lens is measured according to proceduresdescribed in U.S. Pat. No. 5,760,100 (herein incorporated by referencein its entirety. The values of ion permeability reported in thefollowing examples are relative ionoflux diffusion coefficients(D/D_(ref)) in reference to a lens material, Alsacon, as referencematerial. Alsacon has an ionoflux diffusion coefficient of 0.314×10⁻³mm²/minute.

Lubricity Evaluation

The lubricity rating is a qualitative ranking scheme where 0 is assignedto control lenses coated with polyacrylic acid, 1 is assigned toOasys™/TruEye™ commercial lenses and 4 is assigned to commercial AirOptix™ lenses. The samples are rinsed with excess DI water for at leastthree times and then transferred to PBS before the evaluation. Beforethe evaluation, hands are rinsed with a soap solution, extensivelyrinsed with DI water and then dried with KimWpe® towels. The samples arehandled between the fingers and a numerical number is assigned for eachsample relative to the above standard lenses described above. Forexample, if lenses are determined to be only slightly better than AirOptix™ lenses, then they are assigned a number 3. For consistency, allratings are independently collected by the same two operators in orderto avoid bias and the data reveal good qualitative agreement andconsistency in the evaluation.

Surface WettabilityTests.

Water contact angle on a contact lens is a general measure of thesurface wettability of the contact lens. In particular, a low watercontact angle corresponds to more wettable surface. Average contactangles (Sessile Drop) of contact lenses are measured using a VCA 2500 XEcontact angle measurement device from AST, Inc., located in Boston,Mass. This equipment is capable of measuring advancing or recedingcontact angles or sessile (static) contact angles. The measurements areperformed on fully hydrated contact lenses and immediately afterblot-drying as follows. A contact lens is removed from the vial andwashed 3 times in ˜200 ml of fresh DI water in order to remove looselybound packaging additives from the lens surface. The lens is then placedon top of a lint-free clean cloth (Alpha Wipe TX1009), dabbed well toremove surface water, mounted on the contact angle measurement pedestal,blown dry with a blast of dry air and finally the sessile drop contactangle is automatically measured using the software provided by themanufacturer. The DI water used for measuring the contact angle has aresistivity >18MΩcm and the droplet volume used is 2 μl. Typically,uncoated silicone hydrogel lenses (after autoclave) have a sessile dropcontact angle around 120 degrees. The tweezers and the pedestal arewashed well with Isopropanol and rinsed with DI water before coming incontact with the contact lenses.

Water Break-Up Time (WBUT) Tests.

The surface hydrophilicity of the lenses (after autoclave) is assessedby determining the time required for the water film to start breaking onthe lens surface. Briefly, lenses are removed from the vial and washed 3times in ˜200 ml of fresh DI water in order to remove loosely boundpackaging additives from the lens surface. The lens is removed from thesolution and held with tweezers against a bright light source. The timethat is needed for the water film to break (de-wet) exposing theunderlying lens material is noted visually. Uncoated lenses typicallyinstantly break upon removal from DI water and are assigned a WBUT of 0seconds. Lenses exhibiting WBUT 5 seconds are considered goodhydrophilicity and are expected to exhibit adequate ability to supportthe tear film on-eye.

Coating Intactness Tests.

The intactness of a coating on the surface of a contact lens can betested according to Sudan Black stain test as follow. Contact lenseswith a coating (an LbL coating, a plasma coating, or any other coatings)are dipped into a Sudan Black dye solution (Sudan Black in vitamin Eoil) and then rinsed extensively in water. Sudan Black dye ishydrophobic and has a great tendency to be absorbed by a hydrophobicmaterial or onto a hydrophobic lens surface or hydrophobic spots on apartially coated surface of a hydrophobic lens (e.g., silicone hydrogelcontact lens). If the coating on a hydrophobic lens is intact, nostaining spots should be observed on or in the lens. All of the lensesunder test are fully hydrated.

Tests of Coating Durability.

The lenses are digitally rubbed with Solo-care® multi-purpose lens caresolution for 30 times and then rinsed with saline. The above procedureis repeated for a given times, e.g., from 1 to 30 times, (i.e., numberof consecutive digital rubbing tests which imitate cleaning and soakingcycles). The lenses are then subjected to Sudan Black test (i.e.,coating intactness test described above) to examine whether the coatingis still intact. To survive digital rubbing test, there is nosignificantly increased staining spots (e.g., staining spots covering nomore than about 5% of the total lens surface). Water contact angles aremeasured to determine the coating durability.

Determination of Azetidinium Content.

The azetidinium content in PAE can be determined according to one of thefollowing assays.

PPVS assays.

PAE charge density (i.e., azetidinium content) can be determinedaccording to PPVS assay, a colorimetric titration assay where thetitrant is potassium vinyl sulfate (PPVS) and Toluidine Blue is theindicator. See, S-K Kam and J. Gregory, “Charge determination ofsynthetic cationic polyelectrolytes by colloid titration,” in Colloid &Surface A: Physicochem. Eng. Aspect, 159: 165-179 (1999). PPVS bindspositively-charged species, e.g., Toluidine Blue and the azetidiniumgroups of PAE. Decreases in Toluidine Blue absorbance intensities areindicative of proportionate PAE charge density (azetidinium content).

PES-Na Assay.

PES-Na assay is another colorimetric titration assay for determining PAEcharge density (azetidinium content). In this assay, the titrant isSodium-polyethylensulphonate (PES-Na) instead of PPVS. The assay isidentical to the PPVS assay described above.

PCD assays.

PCD assay is a potentiometric titration assay for determining PAE chargedensity (azetidinium content). The titrant isSodium-polyethylensulphonate (PES-Na), PPVS or other titrant. PAE chargeis detected by an electrode, for example using the Mütek PCD-04 ParticleCharge Detector from BTG. The measuring principle of this detector canbe found in BTG's websitehttp://www.btg.com/products.asp?langage=1&appli=5&numProd=357&cat=prod).

Nmr Method.

The active positively charged moiety in PAE is the azetidinium group(AZR). The NMR ratio method is a ratio of the number of AZRgroup-specific protons versus the number of non-AZR related protons.This ratio is an indicator of the charge or AZR density for PAE.

Debris Adhesion Test.

Contact lenses with a highly charged surface can be susceptible toincreased debris adhesion during patient handling. A paper towel isrubbed against gloved hands and then both sides of the lens are rubbedwith the fingers to transfer any debris to the lens surface. The lens isbriefly rinsed and then observed under a microscope. A qualitativerating scale from 0 (no debris adhesion) to 4 (debris adhesionequivalent to a PAA coated control lens) is used to rate each lens.Lenses with a score of “0” or “1” are deemed to be acceptable.

Example 2

Preparation of CE-PDMS Macromer

In the first step, α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane(Mn=2000, Shin-Etsu, KF-6001a) is capped with isophorone diisocyanate(IPDI) by reacting 49.85 g ofα,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with 11.1 g IPDI in150 g of dry methyl ethyl ketone (MEK) in the presence of 0.063 g ofdibutyltindilaurate (DBTDL). The reaction is kept for 4.5 h at 40° C.,forming IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g ofα,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=3000, Shin-Etsu,KF-6002) and 50 g of dry MEK are added dropwise to the IPDI-PDMS-IPDIsolution to which has been added an additional 0.063 g of DBTDL. Thereactor is held for 4.5 h at about 40° C., formingHO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. MEK is then removed under reducedpressure. In the third step, the terminal hydroxyl-groups are cappedwith methacryloyloxyethyl groups in a third step by addition of 7.77 gof isocyanatoethylmethacrylate (IEM) and an additional 0.063 g of DBTDL,forming IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (i.e., CE-PDMS terminated withmethacrylate groups).

Alternate Preparation of CE-PDMS Macromer with Terminal MethacrylateGroups

240.43 g of KF-6001 is added into a 1-L reactor equipped with stirring,thermometer, cryostat, dropping funnel, and nitrogen/vacuum inletadapter, and then dried by application of high vacuum (2×10⁻² mBar).Then, under an atmosphere of dry nitrogen, 320 g of distilled MEK isthen added into the reactor and the mixture is stirred thoroughly. 0.235g of DBTDL is added to the reactor. After the reactor is warmed to 45°C., 45.86 g of IPDI are added through an addition funnel over 10 minutesto the reactor under moderate stirring. The reaction is kept for 2 hoursat 60° C. 630 g of KF-6002 dissolved in 452 g of distilled MEK are thenadded and stirred until a homogeneous solution is formed. About 0.235 gof DBTDL is added, and the reactor is held at about 55° C. overnightunder a blanket of dry nitrogen. The next day, MEK is removed by flashdistillation. The reactor is cooled and 22.7 g of IEM are then chargedto the reactor followed by about 0.235 g of DBTDL. After about 3 hours,an additional 3.3 g of IEM are added and the reaction is allowed toproceed overnight. The following day, the reaction mixture is cooled toabout 18° C. to obtain CE-PDMS macromer with terminal methacrylategroups.

Example 3

Preparation of Lens Formulations

A lens formulation is prepared by dissolving components in 1-propanol tohave the following composition: 33% by weight of CE-PDMS macromerprepared in Example 2, 17% by weight ofN-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24% by weightof N,N-dimethylacrylamide (DMA), 0.5% by weight ofN-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-disteaoyl-sn-glycero-3-phosphoethanolamin, sodium salt)(L-PEG), 1.0% by weight Darocur 1173 (DC1173), 0.1% by weight ofvisitint (5% copper phthalocyanine blue pigment dispersion intris(trimethylsiloxy)silylpropylmethacrylate, TRIS), and 24.5% by weightof 1-propanol.

Preparation of Lenses

Lenses are prepared by cast-molding from the lens formulation preparedabove in a reusable mold, similar to the mold shown in FIGS. 1-6 in U.S.Pat. Nos. 7,384,590 and 7,387,759 (FIGS. 1-6). The mold comprises afemale mold half made of CaF₂ and a male mold half made of PMMA. The UVirradiation source is a Hamamatsu lamp with the WG335+TM297 cut offfilter at an intensity of about 4 mW/cm². The lens formulation in themold is irradiated with UV irradiation for about 25 seconds. Cast-moldedlenses are extracted with isopropanol (or methyl ethyl ketone, MEK),rinsed in water, coated with polyacrylic acid (PAA) by dipping lenses ina propanol solution of PAA (0.1% by weight, acidified with formic acidto about pH 2.5), and hydrated in water. Resultant lenses having areactive PAA-LbL base coating thereon are determined to have thefollowing properties: ion permeability of about 8.0 to about 9.0relative to Alsacon lens material; apparent Dk (single point) of about90 to 100; a water content of about 30% to about 33%; and a bulk elasticmodulus of about 0.60 MPa to about 0.65 MPa.

Example 4

An in-package coating (IPC) saline is prepared by adding 0.2%polyamidoamine-epichlorohydrin (PAE)(Kymene from Ashland as an aqueoussolution and used as received, azetidinium content of 0.46 assayed withNMR) in phosphate buffer saline (PBS hereinafter) (about 0.044 w/w %NaH₂PO₄.H₂O, about 0.388 w/w/% Na₂HPO₄.2H₂O, about 0.79 w/w % NaCl) andthe pH is then adjusted to 7.2-7.4.

Lenses from Example 3 are placed in a polypropylene lens packaging shellwith 0.6 mL of the IPC saline (half of the IPC saline is added prior toinserting the lens). The blister is then sealed with foil and autoclavedfor about 30 minutes at 121° C., forming crosslinked coatings (PAA-x-PAEcoating) on the lenses.

Then the lenses are evaluated for debris adhesion, surface cracking,lubricity, contact angle and water break-up time (WBUT). The test lenses(packaged/autoclaved in the IPC saline, i.e., lenses having PAA-x-PAEcoating thereon) show no debris adhesion after being rubbed against apaper towel while control lenses (packaged/autoclaved in PBS, i.e.,lenses having a PAA-LbL base coating thereon) show severe debrisadhesion. The water contact angle (WCA) of the test lenses is low (˜20degrees) but the WBUT is less than 2 seconds. When observed under darkfield microscope, severe cracking lines are visible after handling thelens (lens inversion and rubbing between the fingers). The test lensesare much less lubricous than the control lenses as judged by aqualitative finger-rubbing test.

Example 5

Poly(acrylamide-co-acrylic acid) (or PAAm-PAA or poly(AAm-co-AA) orp(AAm-co-AA)) partial sodium salt (˜80% solid content,Poly(AAm-co-AA)(80/20), Mw. 520,000, Mn 150,000) is purchased fromAldrich and used as received.

An IPC saline is prepared by dissolving 0.02% of Poly(AAm-co-AA)(80/20)and 0.2% of PAE (Kymene from Ashland as an aqueous solution and used asreceived, azetidinium content of 0.46 assayed with NMR) in PBS. The pHis adjusted to 7.2˜7.4. PBS is prepared by dissolving 0.76% NaCl, 0.044%NaH₂PO₄.H₂O and 0.388% Na₂HPO₄.2H₂O in water.

Lenses having a PAA-LbL base coating thereon prepared in Example 3 areplaced in a polypropylene lens packaging shell with 0.6 mL of the IPCsaline (half of the saline is added prior to inserting the lens). Theblister is then sealed with foil and autoclaved for about 30 minutes atabout 121° C. It is believed that a crosslinked coating composed ofthree layers PAA-x-PAE-x-poly(AAm-co-AA) is formed on the lenses duringautoclave.

The test lenses (packaged/autoclaved in the IPC saline, i.e., lenseshaving PAA-x-PAE-x-poly(AAm-co-AA) crosslinked coating thereon) have nodebris adhesion after being rubbed against a paper towel. The testlenses have a WBUT of longer than 10 seconds. When observed under darkfield microscope, cracking lines are visible after rubbing the testlenses. The test lenses are much more lubricous than the test lensesfrom Example 4 but still not as lubricous as the control lenses packagedin PBS.

Example 6

An IPC saline is prepared by dissolving 0.02% of poly(AAm-co-AA) (80/20)and 0.2% of PAE (Kymene from Ashland as an aqueous solution and used asreceived, azetidinium content of 0.46 assayed with NMR) in PBS andadjusting the pH to 7.2˜7.4. Then the saline is then treated by heatingto and at about 70° C. for 4 hours (heat pre-treatment). During thisheat pretreatment, poly(AAm-co-AA) and PAE are partially crosslinkedbetween each other (i.e., not consuming all azetidinium groups of PAE)to form a water-soluble and thermally-crosslinkable hydrophilicpolymeric material containing azetidinium groups within the branchedpolymer network in the IPC saline. After the heat pre-treatment, thefinal IPC saline is filtered using a 0.22 micron polyether sulphone(PES) membrane filter and cooled down back to room temperature.

Lenses having a PAA-LbL base coating thereon prepared in Example 3 areplaced in a polypropylene lens packaging shell with 0.6 mL of the IPCsaline (half of the saline is added prior to inserting the lens). Theblister is then sealed with foil and autoclaved for about 30 minutes atabout 121° C., forming a crosslinked coating (PAA-x-hydrophilicpolymeric material) on the lenses.

The test lenses (packaged in the heat-pretreated IPC saline, i.e.,lenses having PAA-x-hydrophilic polymeric material coating thereon) showno debris adhesion after being rubbed against paper towel while thecontrol lenses (packaged in PBS, i.e., lenses having a non-covalentlyattached layer of PAA thereon) show severe debris adhesion. The testlenses have a WBUT of longer than 10 seconds. When observed under darkfield microscope, no cracking lines are visible after rubbing the testlens. The test lenses are very lubricious in a finger rubbing test andequivalent to the control lenses.

A series of experiments are carried out to study the effects of theconditions (duration and/or temperature) of heat pre-treatment of theIPC saline upon the surface properties of resultant lenses coated withthe IPC saline. Heat treatment times of about 6 hours or longer at about70° C. result in lenses that are susceptible to debris adhesion similarto the control lenses. It is believed that longer preheating treat mayconsume most azetidinium groups and as such numbers of azetidiniumgroups left in the branched polymer network of the resultantwater-soluble polymeric material are insufficient to attach thepolymeric material to the PAA coating. Heat treatment for only 4 hoursat 50° C. results in lenses that show surface cracking lines under darkfield microscopy after being rubbed between the fingers similar to thetest lenses in Example 5 where the IPC saline is not heat pre-treated.It is believed that shorter preheating treat may consume a small amountazetidinium groups and as such numbers of azetidinium groups left in thebranched polymer network of the resultant water-soluble polymericmaterial are high so that the resultant crosslinked coating(PAA-x-hydrophilic polymeric material) on the lenses may have too highcrosslinking density.

Example 7

Poly(acrylamide-co-acrylic acid) partial sodium salt (˜90% solidcontent, poly(AAm-co-AA) 90/10, Mw 200,000) is purchased fromPolysciences, Inc. and used as received.

An IPC saline is prepared by dissolving 0.07% of PAAm-PAA (90/10) and0.2% of PAE (Kymene from Ashland as an aqueous solution and used asreceived, azetidinium content of 0.46 assayed with NMR) in PBS andadjusting the pH to 7.2˜7.4. Then the saline is heat pre-treated forabout 4 hours at about 70° C. (heat pre-treatment). During this heatpretreatment, poly(AAm-co-AA) and PAE are partially crosslinked to eachother (i.e., not consuming all azetidinium groups of PAE) to form awater-soluble and thermally-crosslinkable hydrophilic polymeric materialcontaining azetidinium groups within the branched polymer network in theIPC saline. After the heat pre-treatment, the IPC saline is filteredusing a 0.22 micron polyether sulphone [PES] membrane filter and cooleddown back to room temperature.

Lenses having a PAA-LbL base coating thereon prepared in Example 3 anduncoated Lotrafilcon B lenses (from CIBA VISION CORPORATION) that aredipped into an acidic propanol solution of PAA (ca. 0.1%, pH˜2.5) areplaced in a polypropylene lens packaging shells with 0.6 mL of theheat-pretreated IPC saline (half of the IPC saline is added prior toinserting the lens). The blister is then sealed with foil and autoclavedfor about 30 minutes at 121° C., forming a crosslinked coating(PAA-x-hydrophilic polymeric material) on the lenses.

The test lenses (both Lotrafilcon B and Example 3 lenses having aPAA-x-hydrophilic polymer thereon) have no debris adhesion after beingrubbed against paper towel. The test lenses have a WBUT of longer than10 seconds. When observed under dark field microscope, cracking linesare not visible after rubbing the lenses between the fingers. The lensesare extremely lubricous in qualitative finger rubbing tests.

Example 8

In design of experiments (DOE), IPC salines are produced to contain frombetween about 0.05% and about 0.09% PAAm-PAA and from about 0.075% toabout 0.19% PAE (Kymene from Ashland as an aqueous solution and used asreceived, azetidinium content of 0.46 assayed with NMR) in PBS. The IPCsalines are heat-treated for 8 hours at 60° C. and lenses from Example 3are packaged in the heat-pretreated IPC salines. No differences in thefinal lens surface properties are observed and all lenses showedexcellent lubricity, resistance to debris adhesion, excellentwettability, and no evidence of surface cracking.

Example 9

In design of experiments (DOE), IPC salines are produced to containabout 0.07% PAAm-PAA and sufficient PAE to provide an initialazetidinium content of approximately 8.8 millimole equivalents/Liter(˜0.15% PAE). The heat pre-treatment conditions are varied in a centralcomposite design from 50° C. to 70° C. and the pre-reaction time isvaried from about 4 to about 12 hours. A 24 hour pre-treatment time at60° C. is also tested. 10 ppm hydrogen peroxide is then added to thesalines to prevent bioburden growth and the IPC salines are filteredusing a 0.22 micron polyether sulphone [PES] membrane filter.

Lenses from Example 3 are packaged in the heat-pretreated IPC salinesand the blisters are then autoclaved for 45 minutes at 121° C. Alllenses have excellent lubricity, wettability, and resistance to surfacecracking. Some of the lenses show debris adhesion from paper towels asindicated in Table 1.

TABLE 1 Debris Adhesion Evaluation Temperature (° C.) Time (hrs) 50 5560 65 70 4 pass 6 pass pass 8 pass pass fail 10 pass fail 12 pass 24fail

Example 10

Copolymers of methacryloyloxyethyl phosphorylcholine (MPC) with onecarboxyl-containing vinylic monomer (CH₂═CH(CH₃)C(O)OC₂H₄OC(O)C₂H₄COOH(MS), methacrylic acid (MA)) in the absence or presence ofbutylmethacrylate (BMA) are evaluated in an in-package coating systemsin combination with PAE.

PBS containing NaCl (0.75% by weight), NaH₂PO₄.H₂O (0.0536% by weight),Na₂HPO₄.2H₂O (0.3576% by weight) and DI water (97.59% by weight) isprepared and 0.2% PAE (polycup 3160) is added. The pH is adjusted toabout 7.3.

0.25% of one of several MPC copolymers is then added to form an IPCsaline and the IPC saline is heat pre-treated at 70° C. for 4 hours(heat pre-treatment). During this heat pretreatment, MPC and PAE arepartially crosslinked to each other (i.e., not consuming all azetidiniumgroups of PAE) to form a water-soluble and thermally-crosslinkablehydrophilic polymeric material containing azetidinium groups within thebranched polymer network in the IPC saline. After 4 hours, theheat-pretreated IPC saline is filtered through 0.2 micron Polyethersulphone [PES} membrane filters (Fisher Scientific catalog#09-741-04,Thermo Scientific nalgene #568-0020 (250 ml).

Lenses having a PAA-LbL base coating thereon prepared in Example 3 arepackaged in the heat-pretreated IPC saline and autoclaved for about 30minutes at 121° C. Table 2 shows that all lenses possess excellentsurface properties.

TABLE 2 Wettability MPC Copolymer* D.A. Cracking Lubricity WBUT (sec.)Poly(MPC/MA) 90/10 pass pass excellent excellent Poly(MPC/BMA/MA) passpass excellent excellent 40/40/20 Poly(MPC/BMA/MA) pass pass excellentexcellent 70/20/10 Poly(MPC/BMA/MS) pass pass excellent excellent70/20/10 *The numbers are molar percents of monomer units in thecopolymer. D.A. = Debris Adhesion WBUT is longer than 10 seconds.

Example 11

PAA-Coated Lenses.

Lenses cast-molded from a lens formulation prepared in Example 3according to the molding process described in Example 3 are extractedand coated by dipping in the following series of baths: 3 MEK baths (22,78 and 224 seconds); DI water bath (56 seconds); 2 baths of PAA coatingsolution (prepared by dissolving 3.6 g of PAA (M.W.: 450 kDa, fromLubrizol) in 975 ml of 1-propanol and 25 ml of formic acid) for 44 and56 seconds separately; and 3 DI water baths each for 56 seconds.

PAE/PAA-Coated Lenses.

The above-prepared lenses with a PAA base coating thereon are dippedsuccessively into the following baths: 2 baths of PAE coating solution,which is prepared by dissolving 0.25 wt % of PAE (Polycup 172, fromHercules) in DI water and adjusting the pH to about 5.0 using sodiumhydroxide and finally filtering the resultant solution using a 5 umfilter, for 44 and 56 seconds respectively; and 3 baths of DI water eachfor 56 seconds. After this treatment, the lenses have one layer of PAAand one layer of PAE.

Lenses with PAA-x-PAE-x-CMC Coatings Thereon.

One batch of lenses with one layer of PAA and one layer of PAE thereonare packaged in a 0.2% Sodium carboxymethylcellulose (CMC, Product#7H3SF PH, Ashland Aqualon) in phosphate buffer saline (PBS) and the pH isthen adjusted to 7.2-7.4. The blisters are then sealed and autoclavedfor about 30 minutes at 121 C, forming crosslinked coatings(PAA-x-PAE-x-CMC) on the lenses.

Lenses with PAA-x-PAE-x-HA Coatings Thereon.

Another batch of lenses with one layer of PAA and one layer of PAEthereon are packaged in 0.2% Hyaluronic acid (HA, Product#6915004,Novozymes) in phosphate buffer saline (PBS) and the pH is then adjustedto 7.2-7.4. The blisters are then sealed and autoclaved for about 30minutes at 121 C, forming crosslinked coatings (PAA-x-PAE-x-HA) on thelenses.

The resultants lenses either with PAA-x-PAE-x-CMC coating or withPAA-x-PAE-x-HA coating thereon show no Sudan black staining, no debrisadhesion, and no cracking under microscopy examination. The lenses withPAA-x-PAE-x-CMC coating thereon have an average contact angle of 30±3degrees, while the lenses PAA-x-PAE-x-HA coating thereon have an averagecontact angle of 20±3 degrees.

Example 12

IPC solution preparation. A reaction mixture is prepared by dissolving2.86% by weight of mPEG-SH 2000 (Methoxy-Poly(Ethylene Glycol)-Thiol,Avg MW 2000, Product #MPEG-SH-2000, Laysan Bio Inc.) along with 2% byweight of PAE (Kymene from Ashland as an aqueous solution and used asreceived, azetidinium content of 0.46 assayed with NMR) in PBS and thefinal pH adjusted to 7.5. The solution is heat-treated for about 4 hoursat 45° C. (heat pre-treatment). During this heat pretreatment, mPEG-SH2000 and PAE are reacted with each other to form a water-soluble andthermally-crosslinkable hydrophilic polymeric material containingazetidinium groups and chemically-grafted polyethyleneglycol polymerchains. After the heat-treatment, the solution is diluted with 10-foldPBS containing 0.25% sodium citrate, pH adjusted to 7.2˜7.4, and thenfiltered using 0.22 micron polyether sulphone (PES) membrane filter. Thefinal IPC saline contains 0.286% by weight of hydrophilic polymericmaterial (consisting of about 59% by weight of MPEG-SH-2000 chains andabout 41% by weight of PAE chains) and 0.25% Sodium citrate dihydrate.The PBS is prepared by dissolving 0.74% NaCl, 0.053% NaH₂PO₄.H₂O and0.353% Na₂HPO₄.2H₂O in water. Lenses with crosslinked coatings thereon.PAA-coated lenses from Example 11 are packaged in the above IPC salinein polypropylene lens packaging shells and then autoclaved for about 30minutes at about 121° C., forming a crosslinked coating on the lenses.

The final lenses show no debris adhesion, no cracking lines afterrubbing the lens. The lenses are very lubricious in a finger rubbingtest comparable to control PAA-coated lenses.

A series of experiments are carried out to study the effects of theconditions (reaction time and solution concentration of mPEG-SH2000(with constant PAE concentration 2%) upon the surface properties of theresultant lenses coated with the IPC saline. The results are shown inTable 3.

TABLE 3 [mPEG- Reaction Lubricity SH2000]¹ time @ Test Test (wt %) 45°C. (hr) D.A. Cracking 1 2 WCA 2.86 0 0, 2  0, 2; 2, NA 3 3 17 2.86 0.50, 0 0, 2; 0, 2 2-3 2 21 2.86 2 0, 0 0, 0; 0, 0 2 2 20 2.86 4 0, 0 0, 0;0, 0 1-2 1 37 0.5 4 0 0, 2; NA  4 3-4 15 1.5 4 0 0, 0; NA  3 3 20 6 4 00, 0; NA  0-1 0 51 D.A. = debris adhesion; WCA = water contact angle.¹PAE concentration: 2% by weight.

As the solution concentration of mPEGSH2000 increases, the lenslubricity increases accordingly. It is believed that the increase in thecontact angle of the surface may be due to the increasing density ofterminal methyl groups on the surface with increasing grafting density.At high grafting densities, corresponding to a solution concentration of0.6%, the contact angle approaches measurements obtained on Polyethyleneglycol (PEG) monolayer grafted flat substrates (Reference: Langmuir2008, 24, 10646-10653).

Example 13

A series of experiments are carried out to study the effects ofmolecular weight of the mPEG-SH. The IPC saline is prepared similar tothe procedure described in Example 12. However, the following mPEG-SHare used to prepare the saline: mPEG-SH 1000, mPEG-SH 2000, mPEG-SH 5000and mPEG-SH 20000. All the salines are subjected to heat treatment at45° C. for 4 hours and 10-fold dilution. The results and the reactionconditions are shown below:

mPEG-SH M.W. Conc. Lubricity (Daltons) (%)* D.A. Cracking Test 1 Test 2WCA 1000 1.5 No No 2 1 21 1000 2.86 No No 1 1 27 2000 1.5 No No 2 2 282000 2.86 No No 0-1 0 21 5000 1.5 No No 2 2 18 5000 2.86 No No 0-1 0-126 20000 1.5 No No 3 2 21 20000 2.86 No No 2 1 21 D.A. = debrisadhesion; WCA = water contact angle. *The initial concentration ofMPEG-SH in the IPC saline with 2% PAE therein before the heatpretreatment and the 10-fold dilution.

Example 14

A reaction mixture is prepared by dissolving 2.5% of mPEG-SH 2000, 10%of PAE (Kymene from Ashland as an aqueous solution and used as received,azetidinium content of 0.46 assayed with NMR) in PBS and 0.25% of sodiumcitrate dihydrate. The pH of this solution is then adjusted to 7.5 andalso degassed by bubbling nitrogen gas through the container for 2hours. This solution is later heat treated for about 6 hours at 45° C.forming a thermally crosslinkable hydrophilic polymeric materialcontaining mPEG-SH-2000 groups chemically grafted onto the polymer byreaction with the Azetidinium groups in PAE. After the heat-treatment,the solution is diluted 50-fold using PBS containing 0.25% sodiumcitrate, pH adjusted to 7.2˜7.4, and then filtered using 0.22 micronpolyether sulphone (PES) membrane filter. The final IPC saline containsabout 0.30% by weight of the polymeric material (consisting of about 17%wt. mPEG-SH-2000 and about 83% wt. PAE) and 0.25% Sodium citratedihydrate.

PAA-coated lenses from Example 11 are packaged in the above IPC salinein polypropylene lens packaging shells and then autoclaved for about 30minutes at about 121° C., forming a crosslinked coating on the lenses.

The final lenses show no debris adhesion, no cracking lines afterrubbing the lens. The test lenses are very lubricious in a fingerrubbing test comparable to control PAA-coated lenses.

Example 15

A reaction mixture is prepared by dissolving 3.62% of mPEG-NH₂ 550(methoxy-poly(ethyleneglycol)-amine, M.W.˜550 (Product #MPEG-NH₂-550,Laysan Bio Inc.) along with 2% of PAE (Kymene from Ashland as an aqueoussolution and used as received, azetidinium ratio of 0.46 assayed withNMR) in PBS and the final pH adjusted to 10. The solution isheat-treated for about 4 hours at 45° C. forming a thermallycrosslinkable hydrophilic polymeric material containing MPEG-NH₂-550groups chemically grafted onto the polymer by reaction with theazetidinium groups in PAE. After the heat-treatment, the solution isdiluted with 10-fold PBS containing 0.25% sodium citrate, pH adjusted to7.2˜7.4, and then filtered using 0.22 micron polyether sulphone (PES)membrane filter. The final IPC saline contains about 0.562% wt. ofpolymeric material (consisting of 64% wt. MPEG-SH-2000 and about 36% wt.PAE) and 0.25% Sodium citrate dihydrate. PBS is prepared by dissolving0.74% NaCl, 0.053% NaH₂PO₄.H₂O and 0.353% Na₂HPO₄.2H₂O in water.

PAA-coated lenses from Example 11 are packaged in the above IPC salinein polypropylene lens packaging shells and then autoclaved for about 30minutes at about 121° C., forming a crosslinked coating on the lenses.

The final lenses show no debris adhesion, and no cracking lines areobserved after digitally (finger) rubbing the lens.

Example 16

Poloxamer 108 (sample) and nelfilcon A (CIBA VISION) are used asreceived. Nelfilcon A is a polymerizable polyvinyl alcohol obtained bymodifying a polyvinyl alcohol (e.g., Gohsenol KL-03 from Nippon Gohseior the like) with N-(2,2-Dimethoxyethyl)acrylamide under cyclic-acetalformation reaction conditions (Buhler et al., CHIMIA, 53 (1999),269-274, herein incorporated by reference in its entirety). About 2.5%of vinyl alcohol units in nelfilcon A is modified byN-(2,2-Dimethoxyethyl)acrylamide.

IPC saline is prepared by dissolving 0.004% poloxamer 108, 0.8%nelfilcon A, 0.2% PAE (Kymene, Polycup 3160), 0.45% NaCl, and 1.1%Na₂HPO₄.2H₂O in DI water. The saline is heat pre-treated by stirring for2 hrs at about 65-70° C. After heated pre-treatment, the saline isallowed to cool to room temperature and then filtered using a 0.2 μm PESfilter.

Lenses prepared in Example 3 are placed in a polypropylene lenspackaging shell with 0.6 mL of the IPC saline (half of the saline isadded prior to inserting the lens). The blister is then sealed with foiland autoclaved for about 30 minutes at 121° C.

The test lenses show no debris adhesion after being rubbed against papertowel. The lenses had a WBUT of >10 seconds. When observed under darkfoiled microscope, cracking lines are not visible after rubbing thelenses between the fingers. The lens is much more lubricous than thelenses from Example 4 but still not as lubricous as the PAA coatedcontrol lenses packaged in PBS.

Example 17

A. Synthesis of 80% Ethylenically-Functionalized Chain-ExtendedPolysiloxane

KF-6001A (α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=2000,from Shin-Etsu) and KF-6002A(α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=3400, fromShin-Etsu) are separately dried at about 60° C. for 12 hours (orovernight) under high vacuum in a single neck flask. The OH molarequivalent weights of KF-6001A and KF-6002A are determined by titrationof hydroxyl groups and are used to calculate the millimolar equivalentto be used in the synthesis.

A one-liter reaction vessel is evacuated overnight to remove moisture,and the vacuum broken with dry nitrogen. 75.00 g (75 meq) of driedKF6001A is charged to the reactor, and then 16.68 g (150 meq) of freshlydistilled IPDI is added into the reactor. The reactor is purged withnitrogen and heated to 45° C. with stirring and then 0.30 g of DBTDL isadded. The reactor is sealed, and a positive flow of nitrogen ismaintained. An exotherm occurs, after which the reaction mixture isallowed to cool and stir at 55° C. for 2 hours. After reaching theexotherm, 248.00 g (150 meq) of dried KF6002A is added to the reactor at55° C. and then 100 μL of DBTDL is added. The reactor is stirred forfour hours. Heating is discontinued and the reactor is allowed to coolovernight. The nitrogen bubble is discontinued and the reactor is openedto atmosphere for 30 minutes with moderate stirring. Ahydroxyl-terminated chain-extended polysiloxane having 3 polysiloxanesegments, HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH), is formed.

For 80% ethylenically-functionalized polysiloxane, 18.64 g (120 meq) ofIEM is added to the reactor, along with 100 μL of DBTDL. The reactor isstirred for 24 hours, and then product (80% IEM-capped CE-PDMS) isdecanted and stored under refrigeration.

B: Synthesis of Non-UV-Absorbing Amphiphilic Branched PolysiloxanePrepolymer

A 1-L jacketed reactor is equipped with 500-mL addition funnel, overheadstirring, reflux condenser with nitrogen/vacuum inlet adapter,thermometer, and sampling adapter. The reactor is charged with 45.6 g of80% IEM-capped CE-PDMS prepared above and sealed. A solution of 0.65 gof hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, 27.80 g of(tris(trimethylsilyl))-siloxypropyl)methacrylate (TRIS), in 279 g ofethyl acetate is charged to the addition funnel. The reactor is degassedat <1 mbar for 30 minutes at RT with a high-vacuum pump. The monomersolution is degassed at 100 mbar and RT for 10 minutes for three cycles,breaking vacuum with nitrogen between degas cycles. The monomer solutionis then charged to the reactor, and then the reaction mixture is stirredand heated to 67° C. While heating, a solution of 1.50 g ofmercaptoethanol (chain transfer agent, CTA) and 0.26 g ofazoisobutyronitrile dissolved in 39 g of ethyl acetate is charged to theaddition funnel and deoxygenated three times at 100 mbar, RT for 10minutes. When the reactor temperature reaches 67° C., the initiator/CTAsolution is added to the PDMS/monomer solution in the reactor. Thereaction is allowed to proceed for 8 hours, and then heating isdiscontinued and reactor temperature is brought to room temperaturewithin 15 minutes.

The resultant reaction mixture then is siphoned to a dry single-neckflask with airtight lid, and 4.452 g of IEM is added with 0.21 g ofDBTDL. The mixture is stirred 24 hs at room temperature, formingnon-UV-absorbing amphiphilic branched polysiloxane prepolymer. To thismixture solution, 100 uL of hydroxy-tetramethylene piperonyloxy solutionin ethyl acetate (2 g/20 mL) is added. The solution is then concentratedto 200 g (˜50%) using rota-yap at 30° C. and filtered through 1 um poresize filter paper. After solvent exchange to 1-propanol, the solution isfurther concentrated to the desired concentration.

C. Synthesis of UV-Absorbing Amphiphilic Branched PolysiloxanePrepolymer

A 1-L jacketed reactor is equipped with 500-mL addition funnel, overheadstirring, reflux condenser with nitrogen/vacuum inlet adapter,thermometer, and sampling adapter. The reactor is then charged with45.98 g of 80% IEM-capped CE-PDMS prepared above and the reactor issealed. A solution of 0.512 g of HEMA, 25.354 g of DMA, 1.38 g ofNorbloc methacrylate, 26.034 g of TRIS, in 263 g of ethyl acetate ischarged to the addition funnel. The reactor is degassed at <1 mbar for30 minutes at RT with a high-vacuum pump. The monomer solution isdegassed at 100 mbar and RT for 10 minutes for three cycles, breakingvacuum with nitrogen between degas cycles. The monomer solution is thencharged to the reactor, and then the reaction mixture is stirred andheated to 67° C. While heating, a solution of 1.480 g of mercaptoethanol(chain transfer agent, CTA) and 0.260 g of azoisobutyronitrile dissolvedin 38 g of ethyl acetate is charged to the addition funnel anddeoxygenated three times at 100 mbar, room temperature for 10 minutes.When the reactor temperature reaches 67° C., the initiator/CTA solutionis added to the PDMS/monomer solution in the reactor. The reaction isallowed to proceed for 8 hours, and then heating is discontinued andreactor temperature is brought to room temperature within 15 min.

The resultant reaction mixture then is siphoned to a dry single-neckflask with airtight lid, and 3.841 g of isocyanatoethyl acrylate isadded with 0.15 g of DBTDL. The mixture is stirred 24 hs at roomtemperature, forming a UV-absorbing amphiphilic branched polysiloxaneprepolymer. To this mixture solution, 100 uL of hydroxy-tetramethylenepiperonyloxy solution in ethyl acetate (2 g/20 mL) is added. Thesolution is then concentrated to 200 g (˜50%) using rota-yap at 30° C.and filtered through 1 um pore size filter paper.

D-1: Lens Formulation with Non-UV-Absorbing Polysiloxane Prepolymer

In a 100 mL amber flask, 4.31 g of synthesized macromer solution (82.39%in 1-propanol) prepared above is added. In a 20 mL vial, 0.081 g of TPOand 0.045 g of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) aredissolved in 10 g of 1-propanol and then transferred to the macromersolution. After the mixture is concentrated to 5.64 g using rota-yap at30° C., 0.36 g of DMA is added and the formulation is homogenized atroom temperature. 6 g of clear lens formulation D-1 is obtained.

D-2: Lens Formulation with UV-Absorbing Polysiloxane Prepolymer (4% DMA)

In a 100 mL amber flask, 24.250 g of macromer solution prepared above(43.92% in ethyl acetate) is added. In a 50 mL vial, 0.15 g of TPO and0.75 g of DMPC is dissolved in 20 g of 1-propanol and then transferredto the macromer solution. 20 g of solvent is pulled off using rota-yapat 30° C., followed by addition of 20 g of 1-propanol. After two cycles,the mixture is concentrated to 14.40 g. 0.6 g of DMA is added to thismixture and the formulation is homogenized at room temperature. 15 g ofclear lens formulation D-2 is obtained.

D-3: Lens Formulation with UV-Absorbing Polysiloxane Prepolymer (2%DMA/2% HEA)

In a 100 mL amber flask, 24.250 g of macromer solution prepared above(43.92% in ethyl acetate) is added. In a 50 mL vial, 0.15 g of TPO and0.75 g of DMPC is dissolved in 20 g of 1-propanol and then transferredto the macromer solution. 20 g of solvent is pulled off using rota-yapat 30° C., followed by addition of 20 g of 1-propanol. After two cycles,the mixture is concentrated to 14.40 g. 0.3 g of DMA and 0.3 g of HEA isadded to this mixture and the formulation is homogenized at roomtemperature. 15 g of clear lens formulation D-3 is obtained.

Example 18 Example E: Covalent Attachment of Modified PAE CoatingPolymers

Monomers containing amine groups, N-(3-Aminopropyl)methacrylamidehydrochloride (APMAA-HCl) or N-(2-aminoethyl) methacrylamidehydrochloride (AEMAA-HCl) are purchased from Polysciences and used asreceived. Poly(amidoamine epichlorohydrine) (PAE) is received fromAshland as an aqueous solution and used as received.Poly(acrylamide-co-acrylic acid) (poly(AAm-co-AA) (90/10) fromPolysciences, mPEG-SH from Laysan Bio, and poly(MPC-co-AeMA) (i.e., acopolymer of methacryloyloxyethyl phosphorylcholine (MPC) andaminoethylmethacrylate (AeMA)) from NOF are used as received.

APMAA-HCl monomer is dissolved in methanol and added to the lensformulations D-1, D-2 and D-3 (prepared in Example 17) to achieve a 1 wt% concentration.

Reactive packaging saline is prepared by dissolving the componentslisted in Table 4 along with appropriate buffer salts in DI water. Thesaline is heat pre-treated by stirring for 8 hrs at about 60° C. Afterheated pre-treatment, the saline is allowed to cool to room temperatureand then filtered using a 0.2 μm PES filter.

TABLE 4 Package Saline Sample 1 2 3 4 5 pH 7.4 7.4 7.4 8 8 PAE  0.2%0.2% 0.2% 0.2% 0.2% Poly(AAm-co-AA) (90/10) 0.07% 0.2% — — — mPEG-SH, Mw= 2000 — — 0.3% — — mPEG-SH, Mw = 10000 — — — 0.2% — Poly(MPC-Co-AeMA)(90/10) — — — — 0.2%

Lens formulation D-1 prepared in Example 17 is modified by addition ofthe APMAA-HCl monomer (stock solution of APMMA-HCL in 1:1methanol:propanol) and cured at 16 mW/cm² with 330 nm filter. LensFormulations D-2 and D-3 prepared in Example 17 are modified by additionof the APMAA-HCl monomer and cured at 4.6 mW/cm² with 380 nm filter.

DSM Lenses.

Female portions of polypropylene lens molds are filled with about 75microliters of a lens formulation prepared as above, and the molds areclosed with the male portion of the polypropylene lens molds (base curvemolds). Contact lenses are obtained by curing the closed molds for about5 minutes with an UV irradiation source (Hamamatsu lamp with a 330nm-cut-off filter at an intensity of about 16 mW/cm².

LS lenses. LS lenses are prepared by cast-molding from a lensformulation prepared as above in a reusable mold, similar to the moldshown in FIGS. 1-6 in U.S. Pat. Nos. 7,384,590 and 7,387,759 (FIGS.1-6). The mold comprises a female mold half made of CaF₂ and a male moldhalf made of PMMA. The UV irradiation source is a Hamamatsu lamp with a380 nm-cut-off filter at an intensity of about 4.6 mW/cm². The lensformulation in the mold is irradiated with UV irradiation for about 30seconds.

Lens formulation D-1 modified with APMAA-HCl is cured according to DSMand LS methods described above, while with lens formulation D-2 or D-3is cured according to the LS method described above.

Molded lenses are extracted in methyl ethyl ketone, hydrated, andpackaged in one of the salines described in Table 4. Lenses are placedin a polypropylene lens packaging shell with 0.6 mL of the IPC saline(half of the saline is added prior to inserting the lens). The blisteris then sealed with foil and autoclaved for 30 min at 121° C.

Evaluation of the lens surface shows that all test lenses had no debrisadhesion after being rubbed against paper towel. When observed underdark-field microscope, cracking lines are not visible after rubbing thelenses between the fingers.

The lens surface wettability (WBUT), lubricity, and contact angle aremeasured and results are summarized in Table 5. The lenses are madeaccording DSM method unless specified otherwise. Lubricity is ratedagainst a qualitative scale from 0 to 5 where lower numbers indicategreater lubricity. In general, all properties are shown to improve afterapplication of the in-package coating.

TABLE 5 Lens formulation for WBUT Contact making lenses Saline¹ (second)Lubricity Angle [°] D1 as control 1 0 4-5 114 (free of APMAA) 3 0 4 119D1 w/1% APMAA 1 10  0-1 104 3 2 0-1  99 D2 as control 1 0 4-5 115 (freeof APMAA) 3 0 3 107 4  0²  3-4²  116² D2 w/1% APMAA 1 5 2-3  90 3 6 1 95 4 5-10²  3²  106² D3 w/1% APMAA 2 9 3-4 103 3 14  2-3  91 4 15  3 54 5 13  2  69 ¹The number is the packaging saline number shown inTable 4. ²LS lenses

Example 19

Preparation of Lens Formulations. A lens formulation is prepared bydissolving components in 1-propanol to have the following composition:about 32% by weight of CE-PDMS macromer prepared in Example 2, about 21%by weight of TRIS-Am, about 23% by weight of DMA, about 0.6% by weightof L-PEG, about 1% by weight of DC1173, about 0.1% by weight of visitint(5% copper phthalocyanine blue pigment dispersion in TRIS), about 0.8%by weight of DMPC, about 200 ppm H-tempo, and about 22% by weight of1-propanol.

Preparation of Lenses.

Lenses are prepared by cast-molding from the lens formulation preparedabove in a reusable mold (quartz female mold half and glass male moldhalf), similar to the mold shown in FIGS. 1-6 in U.S. Pat. Nos.7,384,590 and 7,387,759 (FIGS. 1-6). The lens formulation in the moldsis irradiated with UV irradiation (13.0 mW/cm²) for about 24 seconds.

PAA-Coating Solution.

A PAA coating solution is prepared by dissolving an amount of PAA (M.W.:450 kDa, from Lubrizol) in a given volume of 1-propanol to have aconcentration of about 0.36% by weight and the pH is adjusted withformic acid to about 2.0.

PAA-Coated Lenses.

Cast-molded contact lenses as above are extracted and coated by dippingin the following series of baths: DI water bath (about 56 seconds); 6MEK baths (about 44, 56, 56, 56, 56, and 56 second respectively); DIwater bath (about 56 seconds); one bath of PAA coating solution (about0.36% by weight, acidified with formic acid to about pH 2.0) in 100%1-propanol (about 44 seconds); one bath of a water/1-propanol 50%/50%mixture (about 56 seconds); 4 DI water baths each for about 56 seconds;one PBS bath for about 56 seconds; and one DI water bath for about 56seconds.

IPC saline.

Poly(AAm-co-AA)(90/10) partial sodium salt (˜90% solid content,poly(AAm-co-AA) 90/10, Mw 200,000) is purchased from Polysciences, Inc.and used as received. PAE (Kymene, an azetidinium content of 0.46assayed with NMR) is purchased from Ashland as an aqueous solution andused as received. An IPC saline is prepared by dissolving about 0.07%w/w of poly(AAm-co-AA)(90/10) and about 0.15% of PAE (an initialazetidinium millimolar equivalents of about 8.8 millimole) in PBS (about0.044 w/w % NaH₂PO₄.H₂O, about 0.388 w/w/% Na₂HPO₄.2H₂O, about 0.79 w/w% NaCl) and adjusting the pH to 7.2˜7.4. Then the IPC saline is heatpre-treated for about 4 hours at about 70° C. (heat pretreatment) Duringthis heat pretreatment, poly(AAm-co-AA) and PAE are partiallycrosslinked to each other (i.e., not consuming all azetidinium groups ofPAE) to form a water-soluble and thermally-crosslinkable hydrophilicpolymeric material containing azetidinium groups within the branchedpolymer network in the IPC saline. After the heat pre-treatment, the IPCsaline is filtered using a 0.22 micron PES membrane filter and cooleddown back to room temperature. 10 ppm hydrogen peroxide is then added tothe final IPC saline to prevent bioburden growth and the IPC saline isfiltered using a 0.22 micron PES membrane filter.

Application of Crosslinked Coating.

Lenses having a PAA-LbL base coating thereon prepared above are placedin polypropylene lens packaging shells (one lens per shell) with 0.6 mLof the IPC saline (half of the saline is added prior to inserting thelens). The blisters are then sealed with foil and autoclaved for about30 minutes at about 121° C., forming SiHy contact lenses withcrosslinked coatings (PAA-x-hydrophilic polymeric material) thereon.

Characterization of SiHy Lenses.

The resultant SiHy contact lenses with crosslinked coatings(PAA-x-hydrophilic polymeric material) thereon show no debris adhesionafter being rubbed against paper towel while the control lenses(packaged in PBS, i.e., lenses having a non-covalently attached layer ofPAA thereon) show severe debris adhesion. The lenses have an oxygenpermeability (Dk_(c) or estimated intrinsic Dk) of 146 barrers, a bulkelastic modulus of 0.76 MPa, a water content of about 32% by weight, arelative ion permeability of about 6 (relative to Alsacon lens), acontact angle of from about 34 to 47 degrees, a WBUT of longer than 10seconds. When observed under dark field microscope, no cracking linesare visible after rubbing the test lens. The lenses are very lubriciousin a finger rubbing test and equivalent to the control lenses.

Example 20

SiHy lenses and IPC salines in lens packages after autoclave, which areprepared in Examples 6, 14 and 19, are subjected to followingbiocompatibility studies.

In-Vitro Cytotoxicity Evaluation.

SiHy lenses are evaluated by the USP Direct Contact Material Assay. Lensextracts are evaluated by the USP MEM Elution and ISO CEN Cell GrowthInhibition Assay, and the IPC saline in the packages after autoclave isevaluated by a Modified Elution test. All lens and lens extractsevaluated are well within acceptance criteria for each test and nounacceptable cytotoxicity is observed.

In-Vivo Testing.

ISO Systemic Toxicity in the Mouse shows that there is no evidence ofsystemic toxicity in the mouse with extracts of lenses. ISO OcularIrritation Study in the Rabbit shows that extracts of lenses are notconsidered irritants to the ocular tissue of the rabbit. ISO OcularIrritation Study in the Rabbit shows that the IPC saline in the packagesafter autoclave is not considered an irritant to the ocular tissue ofthe rabbit. Lenses worn in a daily disposable wear mode for 22consecutive days are nonirritating to the rabbit model, and eyes treatedwith test lenses are similar to eyes treated with the control lenses.ISO Sensitization Study (Guinea Pig Maximization Testing of PackagingSolutions) shows that the IPC saline after autoclave do not cause anydelayed dermal contact sensitization in the guinea pig. ISOSensitization Study (Guinea Pig Maximization Testing of Lens Extracts)shows that Sodium chloride and sesame oil extracts of the lenses do notcause delayed dermal contact sensitization in the guinea pig.

Genotoxicity Testing.

When IPC salines from the lens packages and SiHy lens extracts aretested in Bacterial Reverse Mutation Assay (Ames Test), it is found thatthe lens extracts and IPC salines are considered to be nonmutagenic toSalmonella typhimurium test strains TA98, TA100, TA1535 and TA1537 andto Escherichia coli WPuvrA. When SiHy lens extracts are tested inMammalian Erythrocyte Micronucleus Assay, they have no clastogenicactivity and to be negative in the mouse bone marrow micronucleus test.When IPC salines from the lens packages are tested according toChromosome Aberration Test in Chinese Hamster Ovary, the IPC salines arenegative for the induction of structural and numerical chromosomeaberrations assays using CHO cells in both non-activated andS9-activated test systems. When SiHy lens extracts are tested accordingto Cell Gene Mutation Test (Mouse Lymphoma Mutagenesis Assay), the lensextracts are shown to be negative in the Mouse Lymphoma MutagenesisAssay.

Example 21

The surface compositions of preformed SiHy contact lenses (i.e., SiHycontact lens without any coating and prior to applying the PAA basecoating), SiHy contact lenses with PAA coating (i.e., those lensesbefore being sealed and autoclaved in lens packages with the IPCsaline), and SiHy contact lenses with a crosslinked coating thereon, allof which are prepared according to the procedures described in Example19, are determined by characterizing vacuum dried contact lenses withX-ray photoelectron spectroscopy (XPS). XPS is a method for measuringthe surface composition of lenses with a sampling depth of about 10 nm.The surface compositions of three types of lenses are reported in Table6.

TABLE 6 Surface Atomic Composition (%) SiHy Lens C N O F* Si Preformed(without coating) 58.0 6.2 23.0 0.8 12.1 With PAA coating 48.9 1.6 42.12.9 4.5 With crosslinked coating 59.1 10.8 25.4 3.2 1.4 *Fluorine isdetected, mostly likely from surface contamination during vacuum dryingprocess XPS analysis

Table 6 shows that when a PAA coating is applied onto a SiHy lens(preformed without coating), the silicon atomic composition issubstantially reduced (from 12.1% to 4.5%) and the nitrogen atomiccomposition is also reduced (from 6.2% to 1.6%). When a crosslinkedcoating is further applied onto the PAA coating, the surface compositionis predominated by carbon, nitrogen and oxygen, which are the threeatomic composition (excluding hydrogen because XPS does not counthydrogen in the surface composition). Such results indicate that theoutmost layer of the SiHy contact lens with crosslinked coating islikely to be essentially consisting of the hydrophilic polymericmaterial which is the reaction product of poly(AAm-co-AA)(90/10) (60% C,22% 0 and 18% N) and PAE.

The following commercial SiHy lenses which are vacuum-dried are alsosubjected to XPS analysis. The surface compositions of those commercialSiHy contact lenses are reported in Table 7.

TABLE 7 Surface Atomic composition (%) C N O F* Si N&D ® Aqua ™ 68.4 9.118.6 1.5 2.4 Air Optix ® Aqua ™ 67.7 9.9 18.2 1.9 2.4 PureVision ® 58.26.9 26.0 1.1 7.9 Premio ™ 61.1 6.9 23.6 1.8 6.6 Acuvue ® Advance ® 61.14.9 24.9 0.7 8.4 Acuvue ® Oasys ® 61.5 5.0 24.4 0.6 8.5 TruEye ™ 63.24.9 24.2 0.8 7.0 Biofinity ® 46.5 1.4 28.9 5.3 17.9 Avaira ™ 52.4 2.527.8 4.2 13.1 *Fluorine is detected also in Advance, Oasys and TruEyelenses, mostly likely from surface contamination during vacuum dryingprocess XPS analysis

It is found that a SiHy contact lens of the invention has a nominalsilicon content, about 1.4%, in the surface layer, much lower than thoseof commercial SiHy lenses without plasma coatings (Acuvue® Advance®,Acuvue® Oasys®, TruEye™, Biofinity®, Avaira™) and PureVision® (withplasma oxidation) and Premio™ (with unknown plasma treatment), and evenlower the SiHy lenses with a plasma-deposited coating having a thicknessof about 25 nm (N&D® Aqua™ and Air Optix® Aqua™). This very low value ofSi % is comparable to the silicon atomic percentage of a control sample,polyethylene from Goodfellow (LDPE, d=0.015 mm; LS356526 SDS;ET31111512; 3004622910). Those results indicate that the very low valuein the XPS analysis of vacuum dried SiHy contact lens of the inventionmay be due to contaminants introduced during the preparation processincluding vacuum drying process and XPS analysis, similar to theobserved fluorine content in the non-fluorine-containing lenses.Silicone has been successfully shielded from XPS analysis in the SiHycontact lenses of the invention.

XPS analysis of SiHy contact lenses of the invention (prepared accordingto the procedures described in Example 19), commercial SiHy contactlenses (CLARITI™ 1 Day, ACUVUE® TruEye™ (narafilcon A and narafilconB)), polyethylene sheets from Goodfellow (LDPE, d=0.015 mm; LS356526SDS; ET31111512; 3004622910), DAILIES® (polyvinylalcohol hydrogellenses, i.e., non-silicone hydrogel lenses), ACUVUE® Moist(polyhydroxyethylmethacrylate hydrogel lenses, i.e., non-siliconehydrogel lenses) is also carried out. All lenses are vacuum-dried.Polyethylene sheets, DAILIES® and ACUVUE® Moist are used as controlbecause they do not contain silicon. The silicon atomic compositions inthe surface layers of the test samples are as following: 1.3±0.2(polyethylene sheet); 1.7±0.9 (DAILIES®); 2.8±0.9 (ACUVUE® Moist);3.7±1.2 (three SiHy lenses prepared according to the proceduresdescribed in Example 19); 5.8±1.5 (CLARITI™ 1 Day); 7.8±0.1 (ACUVUE®TruEye™ (narafilcon A)); and 6.5±0.1 (ACUVUE® TruEye™ (narafilcon B)).The results for SiHy contact lens of the invention are closer to thoseof the traditional hydrogels than to the silicone hydrogels.

Example 22

Fluorescein Tagged PAA (PAA-F).

PAA-F is synthesized in-house by covalently attaching 5-aminofluoresceinto PAA (Mw 450k). The labeling degree of fluorescein is a few %, forexample, about 2 mole % (or n/(m+n)=2% in the formula shown below)

Preparation of Lenses.

Lenses are prepared by cast-molding from the lens formulation preparedabove in Example 19 in a reusable mold (quartz female mold half andglass male mold half), similar to the mold shown in FIGS. 1-6 in U.S.Pat. Nos. 7,384,590 and 7,387,759 (FIGS. 1-6). The lens formulation inthe molds is irradiated with UV irradiation (13.0 mW/cm²) for about 24seconds.

PAA-F Coating Solution.

A PAA-F coating solution is prepared by dissolving an amount of PAA-Fprepared above in a given volume of 1-PrOH/water (95/5) solvent mixtureto have a concentration of about 0.36% by weight and the pH is adjustedwith formic acid to about 2.0. About 5% water is used in order todissolve PAA-F.

PAA-Coated Lenses.

Cast-molded contact lenses are extracted and coated by dipping in thefollowing series of baths: DI water bath (about 56 seconds); 6 MEK baths(about 44, 56, 56, 56, 56, and 56 second respectively); DI water bath(about 56 seconds); one bath of PAA-F coating solution (about 0.36% byweight, acidified with formic acid to about pH 2.0) in 1-PrOH/water(95/5) solvent mixture (about 44 seconds); one bath of awater/1-propanol 50%/50% mixture (about 56 seconds); 4 DI water bathseach for about 56 seconds; one PBS bath for about 56 seconds; and one DIwater bath for about 56 seconds.

Application of Crosslinked Coating.

Lenses having a PAA-LbL base coating thereon prepared above are placedin polypropylene lens packaging shells (one lens per shell) with 0.6 mLof the IPC saline prepared according to the procedures described inExample 19 (half of the saline is added prior to inserting the lens).The blisters are then sealed with foil and autoclaved for about 30minutes at about 121° C., forming SiHy contact lenses with crosslinkedcoatings (PAA-x-hydrophilic polymeric material) thereon.

Con-Focal Laser Fluorescent Microscopy.

A cross section of a hydrated SiHy lens with crosslinked coating(prepared above) is cut and placed between two glass cover slips and theimage is collected on a con-focal laser fluorescent microscope (model #Zeiss LSM 510 Vis). It is scanned from the front curve side of the lensto the base curve side of the lens, or vice versa. The presence of PAA-Fis shown by the green fluorescence and con-focal laser fluorescencemicroscopic images can be obtained. The examination of the con-focallaser fluorescence microscopic images reveals that the PAA-F rich layeris present on both lens surfaces (anterior and posterior surfaces) andat the peripheral edge, while no PAA-F is observed in the bulk materialof the hydrated lens.

The fluorescence intensity profiles are examined across the lens crosssection along a line passing through both the posterior and anteriorsurfaces and normal to the posterior surface. FIG. 3 shows tworepresentative the fluorescence intensity profiles along two linesacross the lens cross section, one at the point where the lens thicknessis about 100 μm (panel A) and the other at the point where the lensthickness is about 200 μm (panel B). The original points in FIG. 3 arethe center points between the anterior and posterior surfaces along thelines. It can be noticed in FIG. 3 that there is a PAA-F-rich layer nearthe outermost surfaces of the SiHy lens with crosslinked coating, noPAA-F is present at the bulk of the lens, and the coating thickness issimilar on these two cross-sections regardless the thickness of thecross-sections.

The thickness of the PAA-F rich layer (i.e., the sum of the infusiondepth into the outer hydrogel layer and the penetration depth of PAA-Finto the bulk material (i.e., the inner layer)), or the transition layer(for schematic illustration see FIG. 2, the transition layer 115), canbe estimated from the fluorescence intensity profile shown in FIG. 3.The possible thickness of the transition layer (PAA-F-rich layer) isestimated by the distance from zero intensity, after crossing the peakintensity, to zero intensity again. Considering that there are possiblecontribution from unknown factors (such as scattering) to thefluorescence intensity, the minimum layer thickness is the thickness forwhich a florescent intensity of at least 10% of the maximum peakintensity is retained. Based on such estimation, the minimum PAA-F-richlayer thickness could be at least about 5 microns. Note that thethickness for the SiHy lenses with PAA coating of the previous Examplescould be higher, considering the PAA concentration used is 10 timeshigher than the PAA-F concentration used in the experiments here. A lenswith thicker coating can also be prepared by using a dip coating timethat is more than 44 seconds, 44 seconds were the dip coating time forPAA-F used in this experiment. A lens with thicker coating may also beprepared by using PAA of different molecular weight.

Example 23

This example illustrates how to determine the water content of thecrosslinked coating (the two outer hydrogel layers) on a SiHy of theinvention). In an effort to determine the potential water content of thecrosslinked coating of SiHy lenses of Example 19, samples of polymerconsisting of the coating components are prepared for evaluation. Theresulting gels are then hydrated and tested to determine water content.

Solutions are prepared using the two polymeric components of acrosslinked coating formed in Example 19: poly(AAm-co-AA)(90/10) andPAE, to have the following composition: 12.55% w/w of PAE, 6.45% w/w ofpoly(AAm-co-AA)(90/10), and 81% w/w of water. The ratio ofPAE/poly(AAm-co-AA) is identical to that in the IPC saline of Example19, but the individual concentrations of the components are higher toensure a gel is formed during autoclave.

The solution is then autoclaved about 45 minutes at 121° C. after whichthe sample gels. The gel samples are then prepared for water contentdetermination by testing the samples after hydration (n=3). Hydratedsamples are prepared by submerging the gel sample in SoftWear saline forat least about 6 hrs (i.e., hydrated overnight).

Hydrated samples are blotted dry and the mass at hydrated state isrecorded via mass balance. Following the recording of the mass athydrated state, the samples are all placed in a vacuum oven set atapproximately 50° C. and dried under a vacuum of <1 inch Hg overnight.

Dried samples are removed from the vacuum oven after overnight dryingand then measured to record dry mass. Water content is calculated usingthe following relationship:Water content=(wet mass−dry mass)/wet mass×100%The water content of the samples is determined to be 84.6±0.4 w/w %.

It is believed that this water content of this PAE/poly(AAm-co-AA)hydrogel represents the outer hydrogel layer (crosslinked coating) ofthe SiHy contact lenses of Example 19 for the following reasons. First,hydrophobic bulk lens polymers (silicone hydrogel) are reasonablypresumed not to be present in the outer surface layer. This appears tobe a very good assumption based upon the XPS data. According to the XPSdata in Example 21, there is no or very low silicon content at thesurface of the SiHy lens with the crosslinked coating, indicating thatthe outer surface layer is composed almost entirely of the coatingpolymers (PAE and PAAm-PAA). Second, the polyacrylic acid (PAA) basecoating (the transition layer) presumably has a minimal impact on thewater content of the surface layer. This assumption may not be valid.But, if any charged PAA would be present in the outer surface layer, itwould further increase the water content beyond 84.6%. Third, a muchhigher concentration of PAE and PAAm-PAA is needed to producePAE/poly(AAm-co-AA) hydrogel than is used in the IPC saline of Example19. This could result in a higher crosslinking density for thePAE/poly(AAm-co-AA) hydrogel which may give an artificially low watercontent result. It is believed that both the presence of PAA in theouter hydrogel layer and lower crosslinking density due to the lowerconcentration of polymeric materials during crosslinking (in Example 19)may result in an surface layer (outer hydrogel layer) having a watercontent that is even higher than that measured in the tests in thisexample. It can be assumed that the outer coating layer of the SiHycontact lenses of Example 19 comprises at least 80% water and may beeven higher when fully hydrated.

Example 24

An Abbe refractometer is typically used to measure the refractive indexof contact lenses. The refractive index difference between a testinglens and the instrument prism creates a unique angle of total internalreflectance which results in a dark visible shadow line. The angle atwhich this shadow line appears is directly related to the refractiveindex of the testing lens. Most contact lenses (including SiHy contactlenses without coating prepared in Example 19) produce a distinct shadowline in the Abbe refractometer, but SiHy with crosslinked coating (i.e.,the outer hydrogel layers) of Example 19 do not produce a distinctshadow line. It is believed that this phenomenon is due to a decrease inthe refractive index of the lens at the surface compared to the bulk andthe fact that the transition from bulk to surface is not abrupt. It isfurther believed that near the surface of the lens the water contentbegins to increase which results in a localized decrease in therefractive index of the lens. This in effect would create simultaneousshadow lines at multiple angles resulting in a blurred image of theshadow line.

The Abbe data demonstrates that the outer surface layer is characterizedby an increase in the water content near the surface of the lens,consistent with the results described in Example 23.

Example 25

SiHy contact lenses with crosslinked coating (i.e., the outer hydrogellayers) prepared in Example 19 desalinated in ultrapure water, placedindividually in a 50 mL disposable beaker with 50 mL of ultra-pure waterand frozen by placing the beaker in a bath with dry ice and isopropylalcohol. The beakers are wrapped in aluminum foil and placed on a VirTisFreezemobile 35EL with a vacuum pressure of =30 μbar and a condensertemperature of =−70° C. After 24 hours the aluminum foil is removed toincrease heat transfer and the flasks are left for another 24-48 hoursfor removal of residual moisture. The flasks are capped to prevent theintroduction of moisture from the air until analyzed. Lens samples arecut in half and two strips are then cut from the middle of each half andmounted on their edges for imaging of cross sections. Samples are thensputter coated with Au/Pd for ˜1 min and exampled by SEM using a BrukerQuantax Microanalysis System (JEOLJSM-800LV SEM). The sample stage istilted ˜0-60° at the discretion of the analyst to obtain the desiredsample orientation.

It is believed that when the SiHy contact lenses are freeze-dried, thehydrated surface structure of the lenses may be preserved or locked tosome degrees. FIG. 4, panel A shows the top view of a SEM image of asurface of a freeze-dried SiHy contact lens prepared in Example 19. Itcan be seen from FIG. 4 that the freeze-dried SiHy contact lens has asponge-like surface structure which would be expected for a high watercontent hydrogel. This result further confirms that a SiHy contact lensof the invention comprises the two outer hydrogel layers of a high watercontent hydrogel. FIG. 4, panels B and C show the side views at twodifferent angles of a cross section of the freeze-dried SiHy contactlens shown in panel A. The panels B and C show the thick inner layerhaving a smooth surface, a transition layer (PAA layer) with a brightercolor on top of the inner layer, and an outer hydrogel layer withsponge-like structures on top of the transition layer. Based on the datashown in the panels B and C, the thickness of the freeze-dried outerhydrogel layer is estimated to be between about 2 μm and 2.5 μm.

Example 26

Fluorescein Tagged Poly(AAm-Co-AA)(90/10) (Referred to as PAAm-PAA-F).

PAAm-PAA-F is synthesized in-house by covalently attaching5-aminofluorescein to PAAm-PAA (90/10), by a procedure similar to thepreparation of PAA-F. Poly(AAm-co-AA)(90/10) partial sodium salt (˜90%solid content, poly(AAm-co-AA) 90/10, Mw 200,000) is purchased fromPolysciences, Inc. and used as received. The labeling degree offluorescein is about 0.04 mole %.

Modified IPC Saline Using PAAm-PAA-F.

This saline is prepared by the same procedure of IPC preparation, asdescribed in Example 19, except where PAAm-PAA is replaced withPAAm-PAA-F.

PAA-Coated Lenses.

Lenses are prepared by cast-molding from the lens formulation preparedabove in Example 19 in a reusable mold (quartz female mold half andglass male mold half), similar to the mold shown in FIGS. 1-6 in U.S.Pat. Nos. 7,384,590 and 7,387,759 (FIGS. 1-6). The lens formulation inthe molds is irradiated with UV irradiation (13.0 mW/cm²) for about 24seconds. Cast-molded contact lenses are extracted and coated by dippingin the following series of baths: DI water bath (about 56 seconds); 6MEK baths (about 44, 56, 56, 56, 56, and 56 second respectively); DIwater bath (about 56 seconds); one bath of PAA coating solution (about0.36% by weight, acidified with formic acid to about pH 2.0) in 1-PrOHsolvent (about 44 seconds); one bath of a water/1-propanol 50%/50%mixture (about 56 seconds); 4 DI water baths each for about 56 seconds;one PBS bath for about 56 seconds; and one DI water bath for about 56seconds.

Application of Crosslinked Coating.

Lenses having a PAA-base coating thereon prepared above are placed inpolypropylene lens packaging shells (one lens per shell) with 0.6 mL ofthe modified IPC saline prepared above using PAAm-PAA-F (half of thesaline is added prior to inserting the lens). The blisters are thensealed with foil and autoclaved for about 30 minutes at about 121° C.,forming SiHy contact lenses with crosslinked coatings (PAA-x-hydrophilicpolymeric material) thereon.

Con-Focal Laser Fluorescent Microscopy.

A piece of a hydrated SiHy lens with crosslinked coating (preparedabove) is placed between two glass cover slips and the image iscollected on a con-focal laser fluorescent microscope (model # Zeiss LSM510 Vis). It is scanned from the front curve side of the lens to thebase curve side of the lens, or vice versa. The presence of PAAm-PAA-Fis shown by the green fluorescence and con-focal laser fluorescencemicroscopic images can be obtained. The examination of the con-focallaser fluorescence microscopic images reveals that the PAAm-PAA-F richlayer (i.e., the outer hydrogel layers) is present on both lens surfaces(anterior and posterior surfaces) and at the peripheral edge, while noPAAm-PAA-F is observed in the bulk material of the lens.

The fluorescence intensity profiles are examined across the lens crosssection along a line passing through both the posterior and anteriorsurfaces and normal to the posterior surface. The thickness of thePAAm-PAA-F rich layer can be estimated from the fluorescence intensityprofile across the lens. The possible thickness of the outer hydrogellayer (PAAm-PAA-F-rich layer) is estimated by the distance from zerointensity, after crossing the peak intensity, to zero intensity again.Considering that there are possible contribution from unknown factors(such as scattering) to the fluorescence intensity, the minimum layerthickness is the thickness for which a florescent intensity of at least10% of the maximum peak intensity is retained. Based on such estimation,the minimum PAAm-PAA-F-rich layer (hydrated outer hydrogel layer)thickness could be at least about 5 microns.

Example 27

Lenses are fabricated using lens formulation D-2 (Example 17) to whichAPMAA monomer has been added to a concentration of 1%. LS lenses areprepared by cast-molding from a lens formulation prepared as above in areusable mold, similar to the mold shown in FIGS. 1-6 in U.S. Pat. Nos.7,384,590 and 7,387,759 (FIGS. 1-6). The mold comprises a female moldhalf made of glass and a male mold half made of quartz. The UVirradiation source is a Hamamatsu lamp with a 380 nm-cut-off filter atan intensity of about 4.6 mW/cm². The lens formulation in the mold isirradiated with UV irradiation for about 30 seconds.

Cast-molded lenses are extracted with methyl ethyl ketone (MEK), rinsedin water, coated with polyacrylic acid (PAA) by dipping lenses in apropanol solution of PAA (0.0044% by weight, acidified with formic acidto about pH 2.5), and hydrated in water.

IPC Saline is prepared according to the composition described in Example9 with pre-reaction conditions of 8 hrs at approximately 60° C. Lensesare placed in a polypropylene lens packaging shell with 0.6 mL of theIPC saline (half of the saline is added prior to inserting the lens).The blister is then sealed with foil and autoclaved for 30 min at 121°C.

Evaluation of the lens surface shows that all test lenses have no debrisadhesion. When observed under dark-field microscope, cracking lines arenot visible after rubbing the lenses between the fingers. The lenssurface wettability (WBUT) is greater than 10 seconds, lubricity israted as “1”, and contact angle is approximately 20°.

Example 28

Cast-molded SiHy contact lenses (without any coating) prepared fromExample 19 are used. All lenses are extracted in MEK overnight to ensureall residual monomer is removed. The first group of lenses (lenses withhydrated crosslinked coating thereon) is soaked overnight in a PAAcoating solution (0.36% by weight of PAA in 1-Propanol, pH 1.7-2.3adjusted with formic acid), while the second group of lenses (control)is soaked in 1-propanol for the same duration. Both groups of lenses arepackaged in the IPC saline prepared in Example 19 and autoclaved. Lensesafter autoclave are tested (in groups of 5) using gravimetric analysistechnique to determine the weights of dry and wet contact lenses (N=14for the first group of contact lenses; N=18 for the second group ofcontact lenses). The results are shown in Table 8.

TABLE 8 Wet Weight Dry Weight (for 5 lens) (for 5 lens) Water Content %Std. Std. Std. Average Dev. Average Dev. Average Dev. 1^(st) Group 0.1440.001 0.0950 0.001 34.2 0.4 2^(nd) Group 0.137 0.001 0.0947 0.002 30.80.4

There is a statically significant difference (7 mg) in wet weightbetween the first and second groups of contact lenses, due to thepresence of the hydrated crosslinked coating the contact lensescomparing with the control lenses (without coating). However, thedifference in dry weight between the first and second groups of contactlenses is about 0.3 mg and is not statistically significant. The lenswater content for the coated lens can be estimated to be ˜96% accordingto the following calculation

$\left( {\frac{W_{1{st}}^{wet} - W_{2{nd}}^{wet}}{\left( {W_{1{st}}^{wet} - W_{2{nd}}^{wet}} \right) + \left( {W_{1{st}}^{dry} - W_{2{nd}}^{dry}} \right)} = {\frac{7\mspace{14mu}{mg}}{{7\mspace{14mu}{mg}} + {0.3\mspace{14mu}{mg}}} \approx {96\%}}} \right).$It is understood that the water content estimated here for thecrosslinked coating on a contact lens may be not accurate because thedifference in dry wet weight between the first and second groups ofcontact lens is too small and even smaller than the standard deviation.

Example 29

This Example illustrates how to quantify the lubricity of SiHy contactlenses according to the inclined plate method (“Derby friction test”).The inclined plate method is a simple test to set-up as shown in FIG. 5.The set up for inclined plate method is composed of a plastic reservoiror tank 501 which is filled with a phosphate buffered saline (PBS,pH˜7.3) 502, a 503 borosilicate glass plate 503 and a shim 506 with anadjustable height between 5 mm and 20 mm height. Both the borosilicateglass plate 503 and the shim 506 are submerged in the phosphate-bufferedsaline 502 in the plastic reservoir or tank 501. In a test, a contactlens 504 is placed on the borosilicate glass plate and then a stainlesssteel ferrule 505 (to provide physiologically relevant pressure).

${{{Critical}\mspace{14mu}{Coefficient}\mspace{14mu}{of}\mspace{14mu}{Friction}} = {\frac{F_{t}}{F_{N}} = {\tan\mspace{14mu}\theta}}},$

in which θ is the critical angle, F_(N) is the normal force, and F_(t)is the tangent force. The highest angle at which a lens continuessliding after being pushed, but stops, or takes longer than 10 seconds,before reaching the end, is defined as the “critical angle θ”. Thecritical coefficient of friction (CCOF) is the tangent of the criticalangle θ. A lens which does not move will be below the CCOF, while a lenswhich does not stop during the travel distance will be above the CCOF.Angles above or below the CCOF are removed from analysis. Derby frictiontest can provide a direct way of measuring the kinematic coefficient offriction.

In the tests according to the inclined plate method, all lenses arestored in PBS solution at least overnight (>6 hours) before testing, inorder to remove any residual packaging solution. The glass plate (6″×4″borosilicate glass) is scrubbed with a soap solution (1% Micro-90) andwiped (AlphaWpe TX1009). Each plate is rinsed thoroughly in DI water,about 2 minutes. A section of the plate friction is tested by fingerrubbing to ensure all soap solution is removed. The water is wiped withpaper towels (KimTech Kimwipe #34705) and inspected under light toensure no foreign particles remain on the glass. The glass plate isplaced on shims of various heights in a plastic reservoir or tank, andthe height of this plane is measured with a micrometer and recorded. Thereservoir is filled with phosphate buffered saline (PBS) to ensure thelens is completely submerged (28 mm depth).

Each lens is placed on the “starting line” and a 0.79 g ferrule (¼″stainless steel to provide physiologically relevant pressure) is droppedonto the lens surface. The lens is allowed to slide down the plate, andthe time the lens took to travel the 96 mm is recorded.

The lens is moved to the starting position with the weight removed priorto retesting. This “pre-loading” effect should be minimized for bestrepeatability. The lens may be tested at multiple angles to obtain theideal CCOF.

Sixteen commercial contact lenses and silicone hydrogel contact lensesprepared in Example 19 are tested for CCOF and the results are reportedin Table 9. The results show that a SiHy contact lens of the invention(prepared in Example 19 to have a crosslinked coating thereon) has thelowest CCOF among any class of silicone hydrogel lenses which arecommercially available and tested, thereby having the highest lubricity.

TABLE 9 Contact lenses SiHy C.H. (mm) C.A. (deg) CCOF Example 19 Y 5.72.2 0.038 DAILIES AquaComfortPlus N 6.0 2.3 0.040 1 Day Acuvue N 6.5 2.50.043 Dailies Aqua N 6.8 2.6 0.045 1-Day Acuvue TruEye Y 7.2 2.8 0.048(narafilcon B) SofLens Daily Disposable N 7.6 2.9 0.051 1-Day AcuvueMoist N 7.7 3.0 0.052 Proclear 1-Day N 8.3 3.2 0.056 1-Day Acuvue TruEyeY 8.8 3.4 0.059 (narafilcon A) Clariti 1-Day Y 9.2 3.5 0.062 AcuvueMoist Y 7.7 2.9 0.051 Air Optix Aqua Y 8.1 3.1 0.054 Biofinity Y 8.1 3.10.054 PureVision Y 9.4 3.6 0.063 Acuvue Advance Y 9.7 3.7 0.065 AcuvueOasys Y 9.9 3.6 0.066 Clariti Y 12.5 4.8 0.084 C.H.: Critical Height;C.A.: Critical angle

Example 30

This Example illustrates how to characterize the negatively-chargedsurface of a SiHy contact lens according to the Positively ChargedParticles Adhesion test.

The surface charge of a lens surface can be detected indirectly via itsinteraction with charged particles or beads. A negatively chargedsurface will attract positively charged particles. A surface free ofnegative charge or substantially free of negative charge will notattract positively charged particles or will attract few positivelycharged particles.

Uncoated SiHy contact lenses (i.e., cast-molded and extracted with MEKas described in Example 19), PAA-coated SiHy contact lenses (as preparedin Example 19), and SiHy contact lenses with a crosslinked coatingthereon (as prepared in Examples 14 and 19) are tested as follows. ThePAA coating of PAA-coated contact lenses has a surface concentration ofcarboxylic groups of about 62.5% by weight (M_(COOH)/M_(AA) in whichM_(COOH) is the mass of carboxylic acid group and M_(AA) is the mass ofacrylic acid). The crosslinked coating of contact lenses of Example 14is theoretically free of carboxylic acid groups, whereas the crosslinkedcoating of contact lenses of Example 19 may contain a low surfaceconcentration of carboxylic acid groups (must be smaller than

$\left. {\frac{0.07{\% \cdot 10}{\% \cdot M_{COOH}}\text{/}M_{AA}}{{0.07\%} + {0.15\%}} \approx {2\%\mspace{14mu}{by}\mspace{14mu}{weight}}} \right).$Lenses are immersed in a dispersion with positively charged particles,after appropriate rinse, the number of particles adhered on the lens isvisualized and estimated or counted.

DOWEX™ 1×4 20-50 Mesh resins are purchased from Sigma-Aldrich and usedas received. DOWEX™ 1×4 20-50 Mesh resins are spherical, Type I strongbase anion resins and are styrene/divinylbenzene copolymer containingN⁺(CH₃)₃Cl⁻ functional groups and 4% divinylbenzene. A 5% of 1×4 20-50Mesh resins are dispersed in PBS and mixed well by stirring or vortexingat approximately 1000 rpm for 10 seconds. Lenses are immersed into thisdispersion and vortexd between rpm 1000-1100 for 1 min, followed byrinsing with DI water and vortex for 1 min. The lenses are then placedin water in glass Petri dishes and images of lenses are taken with Nikonoptical microscope, using bottom lighting. As shown in FIG. 6, almostthe entire surface of PAA-coated lenses is covered with adheredpositively charged particles (FIG. 6a ), whereas a total of about 50positively charged particles are adhered onto lenses with crosslinkedcoating prepared in Example 19 (FIG. 6B) and no positively chargedparticles are adhered onto lenses with crosslinked coating prepared inExample 14 (FIG. 6C). Some loosely adhered particles may fall off thelens surface and can also be found in the water surrounding the lenses.

It is understood that when positively-charged particles with larger size(i.e., DOWEX™ monosphere ion exchange resins, cross-linked polystyrenebeads, chloride form, ˜590 microns in size, from Sigma-Aldrich) are usedin the tests, the number of particles adhered onto the particles can bedecreased. About 30% of these DOWEX monosphere resins are dispersed inPBS. Lenses are immersed into this dispersion for ˜1 min, followed byrinsing with DI water. The lenses are then placed in water in glassPetri dishes and images of lenses are taken with Nikon opticalmicroscope, using bottom lighting. It is found that there are manyparticles (about 200 particles) adhered onto PAA-coated lenses and noparticles are adhered onto lenses with crosslinked coating. Somecommercially available contact lenses are also tested. No particles areobserved on following lenses: Acuvue® TruEye™, Acuvue® Advance®, Acuvue®Oasys®, Avaira™, Biofinity®, Air Optix®, and Focus® Night & Day®.Particles are observed on following 4 types of lenses (in the order ofincreasing number of particles): PureVision®, 1 Day Acuvue® Moist®,Proclear 1 day, Acuvue® (Etafilcon A) lens. Almost the entire surface ofAcuvue® (Etafilcon A) lens is covered with adhered positively chargedparticles.

Negatively charge resins (Amberlite CG50) are purchased from Sigma andused as received. A 5% of this Amberlite CG50 beads is dispersed in PBSand vortexed at about 1000 rpm for 10 seconds. PAA-coated lenses areimmersed into this dispersion and vortexed between rpm 1000-1100 for 1min, followed by rinsing with DI water and vortexed for 1 min. Thelenses are then placed in water in glass Petri dishes and images oflenses are taken with Nikon optical microscope, using bottom lighting.No Amberlite particles (negatively charged) are found on PAA-coatedlenses.

Negatively charged beads (Amberlite CG50), which are coated withpolyethylenimine (PEI, a positively charged electrolytes), are used inthis experiment. The PEI coating procedure is performed as follows. PEI(Lupasol SK, 24% in water, Mw of ˜2000000) is purchased from BASF andused as received. Prepare an aqueous dispersion of 1% Amberliteparticles and 5% PEI. Adjust the pH to 7 and make sure solution iswell-mixed (e.g. by stirring for 30 min). Followed by suspending thedispersion in a large amount of water 2 to 3 times and filtered 2 to 3times before collecting particles (PEI-coated Amberlite). A 5% ofPEI-coated Amberlite CG50 particles are dispersed in PBS and vortexed atabout 1000 rpm for 10 seconds. Lenses are immersed into this dispersionand vortexed between rpm 1000-1100 for 1 min, followed by rinsing withDI water and vortex for 1 min. The lenses are then placed in water inglass Petri dishes and images of lenses are taken with Nikon opticalmicroscope, using bottom lighting. It is observed that there are a lotof PEI-coated Amberlite particles (positively charged particles becauseof the presence of PEI) adhered onto PAA-coated lenses (Example 19).But, there is virtually no PEI-coated Amberlite particles adhered ontouncoated SiHy contact lenses (Example 19), SiHy contact lenses withcrosslinked coating (Example 19), or PAExPAA-coated lenses (Example 4).

Example 31

Sample Preparation:

AFM studies have been conducted on SiHy contact lenses (prepared inExample 19) in hydrated state and in dry state. A lens is removed fromits blister pack (sealed and autoclaved) and a cross-section is cut (forexample by using a razor blade). The cross-section piece of the lens ismounted vertically in a metal clamp, as shown in FIG. 7. A small pieceof lens is sticking out of the top of the holder to allow the AFM tip(above the lens cross section in FIG. 7) to scan it.

AFM Experiment:

Two separate AFM instruments are used to characterize the lens crosssection. In both instances (except for dry samples), the AFM scan isdone under a phosphate buffer solution (PBS with or without NaCl buthaving an osmolarity substantially identical to that of thephysiological saline) to maintain fully hydrated state of the hydrogelsample.

The first AFM instrument is Veeco BioScope AFM with a Nanoscope IVcontroller. Data is collected utilizing triangular silicon cantileverswith a spring constant of 0.58 N/m and a nominal tip radius of curvatureof 20-60 nm. Scans are done in constant contact (force-volume) mode witha probe velocity of 30 microns/second and a force-volume scan rate of0.19 Hz. The topographic data and force-volume data are collectedsimultaneously. Each force curve consisted of about 30 data points. Thelens is fully immersed in PBS during the AFM scan. Normally a scan sizeof maximum of 20 microns is used in order to achieve high enoughresolution for the force-volume image. 128×128 pixels force plots arecollected over about 3 hours per images.

An AFM image of a cross section of a SiHy contact lens with crosslinkedcoating (Example 19) in fully hydrated state is obtained via theForce-Volume method and shown in FIG. 8. In the image the darker coloredregion 420 indicates the coating and the lighter colored region 410indicates the bulk material of the lens. The average thickness of thecrosslinked coating (i.e., the anterior and posterior outer layers) ofthe SiHy contact lens (Example 19) is determined to be about 5.9 μm (st.dev. 0.8 μm) as obtained from 7 images, 4 lenses.

AFM technique enables the determination of the surface modulus (surfacesoftness) at a specific locations on the lens cross section. FIG. 9shows a cross sectional surface modulus profile of a SiHy contact lenswith a crosslinked coating (prepared in Example 19) in fully hydratedstate. Because the surface modulus of a material is proportional to thecantilever deflection, a cross-sectional surface modulus profile of acontact lens can be obtained approximately by plotting the values ofcantilevers deflection (as a measure for the surface modulus of amaterial at a specific location on the lens cross section) as afunctional of the distance from the side (anterior or posterior surface)of the cross section along two lines across the cross section shown inFIG. 8. As shown in FIG. 9, the crosslinked coating (the anterior andposterior outer layers of the contact lens of Example 19) is softer thanthe bulk (inner layer of) silicone hydrogel lens material. Moving alongthe two lines, the surface modulus first remains almost constant with anaverage cantilever deflection of about 52 nm (i.e., average surfacemodulus) over the zone between 0 and about 5.9 microns and thengradually increases at locations further inside lens until reaching amaximum and remains approximately constant thereafter (plateau) with anaverage cantilever deflection of about 91 (i.e., average surfacemodulus) over the zone above about 7 microns. The transition from thesofter crosslinked coating to the harder bulk SiHy material, whichoccurs gradually over the span of a few microns, suggests that agradient in morphology or composition (water content) may be presentbetween the surface of the coating and the bulk of the lens. Surfacemoduli in the zone between 5.9 microns and about 7 microns, i.e., aregion around the border between the outer hydrogel layer and the innerlayer of the silicone hydrogel material, is not used in the calculationof the average surface modulus. It can calculated that the anterior andposterior outer hydrogel layers (crosslinked coating) of the SiHycontact lens (Example 19) has a reduced surface modulus

$\left( {\frac{\overset{\_}{{SM}_{Inner}} - \overset{\_}{{SM}_{Outer}}}{\overset{\_}{{SM}_{Inner}}} \times 100\%} \right.$in which SM_(Outer) is the average surface modulus of the posterior oranterior hydrogel layer, and SM_(Inner) is the average surface modulusof the inner layer) of about 43%.

The SiHy contact lenses (prepared in Example 19) are studied with thesecond AFM instrument. The scanning is done using a Bruker Icon AFM inQuantitative Nanomechanical Measurements (PeakForce QNM) mode usinglenses in either fully-hydrated (PBS without NaCl but with glycerol toreach at the similar osmolarity) or dry state. The lens cross section ismounted in a metal clamp as described above. Test conditions include, aSpring Constant of 1.3 N/m, Tip Radius of 33.3 nm, Sensitivity of 31nm/V, Scan Rate of 0.4 Hz, and a scan Resolution of 512×512.

AFM image of a cross section of the SiHy contact lens (Example 19) infully hydrated state and in dry state are obtained according to thePeakForce QNM method. By analyzing the obtained images, the thickness ofthe crosslinked coating in fully hydrated state is determined to beabout 4.4 microns, while the thickness of the crosslinked coating in drystate is determined to be about 1.2 microns for vacuum dried sample,about 1.6 microns for oven dried sample. The water-swelling ratio

$\left( {\frac{L_{Wet}}{L_{Dry}} \times 100\%} \right.$in which L_(Wet) is the average thickness of the outer hydrogel layer ofthe SiHy contact lens in fully hydrated state, and L_(Dry) is theaverage thickness of that outer hydrogel layer of the SiHy contact lensin dry state) of the crosslinked coating of the SiHy contact lenses(prepared in Example 19) is calculated to be about 277% (oven driedsample) or about 369% (vacuum dried sample).

Example 32

Preparation of Lens Formulations

Formulation I is prepared by dissolving components in 1-propanol to havethe following composition: 33% by weight of CE-PDMS macromer prepared inExample 2, 17% by weight ofN-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24% by weightof N,N-dimethylacrylamide (DMA), 0.5% by weight ofN-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-disteaoyl-sn-glycero-3-phosphoethanolamin, sodium salt)(L-PEG), 1.0% by weight Darocur 1173 (DC1173), 0.1% by weight ofvisitint (5% copper phthalocyanine blue pigment dispersion intris(trimethylsiloxy)silylpropylmethacrylate, TRIS), and 24.5% by weightof 1-propanol.

Formulation II is prepared by dissolving components in 1-propanol tohave the following composition: about 32% by weight of CE-PDMS macromerprepared in Example 2, about 21% by weight of TRIS-Am, about 23% byweight of DMA, about 0.6% by weight of L-PEG, about 1% by weight ofDC1173, about 0.1% by weight of visitint (5% copper phthalocyanine bluepigment dispersion in TRIS), about 0.8% by weight of DMPC, about 200 ppmH-tempo, and about 22% by weight of 1-propanol.

Preparation of Lenses

Lenses are prepared by cast-molding from a lens formulation preparedabove in a reusable mold (quartz female mold half and glass male moldhalf), similar to the mold shown in FIGS. 1-6 in U.S. Pat. Nos.7,384,590 and 7,387,759 (FIGS. 1-6). The UV irradiation source is aHamamatsu lamp with the WG335+TM297 cut off filter at an intensity ofabout 4 mW/cm². The lens formulation in the mold is irradiated with UVirradiation for about 25 seconds. Cast-molded lenses are extracted withmethyl ethyl ketone (MEK) (or propanol or isopropanol).

Application of PAA Prime Coating onto SiHy Contact Lenses

A polyacrylic acid coating solution (PAA-1) is prepared by dissolving anamount of PAA (M.W.: 450 kDa, from Lubrizol) in a given volume of1-propanol to have a concentration of about 0.36% by weight and the pHis adjusted with formic acid to about 2.0.

Another PAA coating solution (PAA-2) is prepared by dissolving an amountof PAA (M.W.: 450 kDa, from Lubrizol) in a given volume of anorganic-based solvent (50/50 1-propanol/H₂O) to have a concentration ofabout 0.39% by weight and the pH is adjusted with formic acid to about2.0.

Above-obtained SiHy contact lenses are subjected to one of dippingprocesses shown in Tables 10 and 11.

TABLE 10 Dipping Process Baths Time 20-0 20-1 20-2 20-3 20-4 20-5 1 56 sH2O H2O H2O H2O H2O H2O 2 44 s MEK MEK MEK MEK MEK MEK 3 56 s MEK MEKMEK MEK MEK MEK 4 56 s MEK MEK MEK MEK MEK MEK 5 56 s MEK MEK MEK MEKMEK MEK 6 56 s MEK MEK MEK MEK MEK MEK 7 56 s MEK MEK MEK MEK MEK MEK 856 s H2O H2O H2O H2O H2O H2O 9 44 s PAA-1 PAA-1 PAA-1 PAA-2 PAA-2 PAA-110 56 s PAA-1 PAA-1 PAA-1 PAA-2 PAA-2 PAA-1 11 56 s H2O PrOH H2O H2O H2OH2O 12 44 s H2O PrOH PrOH PrOH 50/50 50/50 13 56 s H2O H2O H2O H2O H2OH2O 14 56 s H2O H2O H2O H2O H2O H2O 15 56 s PBS PBS PBS PBS PBS PBS 1656 s H2O H2O H2O H2O H2O H2O PrOH represents 100% 1-propanol; PBS standsfor phosphate-buffered saline; MEK stands for methyl ethyl ketone; 50/50stands a solvent mixture of 50/50 1-PrOH/H₂O.

TABLE 11 Dipping Process Baths Time 80-0 80-1 80-2 80-3 80-4 80-5 80-6 156 s H2O H2O H2O H2O H2O H2O H2O 2 44 s MEK MEK MEK MEK MEK MEK MEK 3 56s MEK MEK MEK MEK MEK MEK MEK 4 56 s MEK MEK MEK MEK MEK MEK MEK 5 56 sMEK MEK MEK MEK MEK MEK MEK 6 56 s MEK MEK MEK MEK MEK MEK MEK 7 56 sMEK MEK MEK MEK MEK MEK MEK 8 56 s H2O H2O H2O H2O H2O H2O H2O 9 44 sPAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 PAA-1 10 56 s PAA-1 50/50 PrOH 50/50PrOH PrOH H2O 11 56 s H2O H2O H2O 50/50 PrOH 50/50 50/50 12 44 s H2O H2OH2O H2O H2O H2O H2O 13 56 s H2O H2O H2O H2O H2O H2O H2O 14 56 s H2O H2OH2O H2O H2O H2O H2O 15 56 s PBS PBS PBS PBS PBS PBS PBS 16 56 s H2O H2OH2O H2O H2O H2O H2O PrOH represents 100% 1-propanol; PBS stands forphosphate-buffered saline; MEK stands for methyl ethyl ketone; 50/50stands a solvent mixture of 50/50 1-PrOH/H₂O.Application of Crosslinked Hydrophilic Coating

Poly(acrylamide-co-acrylic acid) partial sodium salt,Poly(AAm-co-AA)(90/10) (˜90% solid content, poly(AAm-co-AA) 90/10, Mw200,000) is purchased from Polysciences, Inc. and used as received. PAE(Kymene, an azetidinium content of 0.46 assayed with NMR) is purchasedfrom Ashland as an aqueous solution and used as received. Anin-package-crosslinking (IPC) saline is prepared by dissolving about0.07% w/w of poly(AAm-co-AA)(90/10) and about 0.15% of PAE (an initialazetidinium millimolar equivalents of about 8.8 millimole) in phosphatebuffered saline (PBS) (about 0.044 w/w % NaH₂PO₄.H₂O, about 0.388 w/w/%Na₂HPO₄.2H₂O, about 0.79 w/w % NaCl) and adjusting the pH to 7.2˜7.4.Then the IPC saline is heat pre-treated for about 4 hours at about 70°C. (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA)and PAE are partially crosslinked to each other (i.e., not consuming allazetidinium groups of PAE) to form a water-soluble andthermally-crosslinkable hydrophilic polymeric material containingazetidinium groups within the branched polymer network in the IPCsaline. After the heat pre-treatment, the IPC saline is filtered using a0.22 micron polyether sulphone [PES] membrane filter and cooled downback to room temperature. 10 ppm hydrogen peroxide is then added to thefinal IPC saline to prevent bioburden growth and the IPC saline isfiltered using a 0.22 micron PES membrane filter.

Lenses having a PAA prime coating thereon prepared above are placed inpolypropylene lens packaging shells (one lens per shell) with 0.6 mL ofthe IPC saline (half of the saline is added prior to inserting thelens). The blisters are then sealed with foil and autoclaved for about30 minutes at about 121° C., forming SiHy contact lenses withcrosslinked hydrophilic coatings thereon.

Characterization of SiHy Lenses.

The resultant SiHy contact lenses with crosslinked hydrophilic coatingsthereon and a center thickness of about 0.95 microns have an oxygenpermeability (Dk_(c) or estimated intrinsic Dk) of about 142 to about150 barrers, a bulk elastic modulus of about 0.72 to about 0.79 MPa, awater content of about 30% to about 33% by weight, a relative ionpermeability of about 6 (relative to Alsacon lens), and a contact angleof from about 34 to about 47 degrees.

Characterization of the Nano-Textured Surfaces of Contact Lens

Transmission-Differential-Interference-Contrast (TDIC) Method.

Contact lenses are placed on a glass slide and flattened by compressingthe lens between the slide and a glass cover slip. Contact lens surfacesare located and examined by focusing through the lens using a NikonME600 microscope with transmission differential interference contrastoptics using a 40× objective lens. The obtained TDIC images are thenevaluated to determine the presence of winkled surface patterns (e.g.,random and/or ordered worm-like patterns, or the likes).

Reflection-Differential-Interference-Contrast (RDIC) Method.

Lenses are placed on a glass slide and flattened by making 4 radial cutsevery ˜90 degrees. Excess saline is blown off the surface usingcompressed air. Lens surface is then examined using Nikon Optiphot-2with reflection differential interference contrast optics for thepresence of winkled surface patterns on the surfaces of a contact lensusing 10×, 20× and 50× objective lenses. A representative image of eachside is acquired using 50× objective lens. The contact lens is thenflipped over, excess saline removed and the other side of the contactlens and is inspected in the same way. The obtained RDIC images are thenevaluated to determine the presence of winkled surface patterns (e.g.,random and/or ordered worm-like patterns, or the likes).

Dark Field Light Microscopy (DFLM).

DFLM is generally based on dark field illumination which is a method ofenhancing contrast in observed samples. This technique consists of alight source outside or blocked from the observer's field of view inorder to illuminate a sample at an angle relative to normal transmittedlight. Since the un-scattered light from the source is not gathered bythe objective lens, it is not part of the image and the background ofthe image appears dark. Since the light source is illuminating thesample at an angle, the light observed in the sample image is that whichis scatted by the sample toward the observer, contrast is then createdbetween this scattered light from the sample and the dark background ofthe image. This contrast mechanism makes dark illumination especiallyuseful for the observation of scattered phenomena such as haze.

DFLM is used to evaluate the haziness of contact lenses as follows. Itis believed that since the dark-field setup involves scattered light,dark-field data could provide the worst-case estimate of haziness. In8-bit grey scale digital images each image pixel is assigned a greyscale intensity (GSI) value in the range from 0-255. Zero represents apixel that is perfectly black and 255 represents a pixel that isperfectly white. An increase in the scattered light captured in theimage will produce pixels with higher GSI values. This GSI value canthen be used as a mechanism to quantify the amount of scattered lightobserved in a dark field image. The haziness is expressed by averagingthe GSI values of all pixels in an area of interest (AOI) (e.g., a wholelens or the lenticular zone or optical zone of a lens). The experimentalset-up consists of a microscope or equivalent optics, an attacheddigital camera and a dark field stand with ring light and variableintensity light source. Optics is designed/arranged so that the entiretyof the contact lens to be observed fills the field of view (typically˜15 mm×20 mm field of view). Illumination is set to a level appropriateto observe the desired changes in the relevant samples. Light intensityis adjusted/calibrated to the same level for each set of samples using adensity/light scattering standard as known to a person skilled in theart. For example, a standard is composed of two overlapping plasticcover slips (identical and slight or moderately frosted). Such standardconsists of areas with three different averaged GSI that include twoareas with intermediate grey scale levels and saturated white (edges).The black areas represent the empty dark field. The black and saturatedwhite areas can be used to verify gain and offset (contrast andbrightness) settings of camera. The intermediate grey levels can providethree points to verify the linear response of the camera. Lightintensity is adjusted so that the average GSI of the empty dark fieldapproaches 0 and that of a defined AOI in a digital image of thestandard is the same each time within ±5 GSI units. After lightintensity calibration, a contact lens is immersed in 0.2 μm-filteredphosphate buffer saline in a quartz Petri dish or a dish or similarclarity which is placed on the DFLM stand. An 8-bit grey scale digitalimage of the lens is then acquired as viewed using the calibratedillumination and the average GSI of a defined AOI within the portion ofthe image containing the lens is determined. This is repeated for asample set of contact lenses. Light intensity calibration isre-evaluated periodically over the course of a test to ensureconsistency. The level of haziness under DFLM examination refers to a

${DFLM}\mspace{14mu}{haziness}\mspace{14mu}\frac{GSI}{255} \times 100{\%.}$

SiHy contact lenses, the PAA prime coating of which is obtainedaccording to either of the dipping processes 20-0 and 80-0, aredetermined to have an averaged DFLM haziness of about 73% and showwrinkle surface patterns (random worm-like patterns) that can bevisually observed by examining the contact lens in hydrated state,according to the method of either RDIC or TDIC as described above. But,the winkled surface patterns have practically no adverse effects uponthe light transmissibility of the contact lenses.

SiHy contact lenses, the PAA prime coating of which is obtainedaccording to either of the dipping processes 20-1 to 20-4, aredetermined to have a low averaged DFLM haziness of about 26% (probablydue to the presence of visitint pigment particles) and show nonoticeable wrinkle surface patterns (random worm-like patterns) whenexamined under either RDIC or TDIC as described above.

A high percentage of SiHy contact lenses, the PAA prime coating of whichis obtained according to either of the dipping process 20-5, aredetermined to have a moderate averaged DFLM haziness of about 45% andshow slightly noticeable wrinkle surface patterns when examined undereither RDIC or TDIC as described above. But, the winkled surfacepatterns have practically no adverse effects upon the lighttransmissibility of the contact lenses.

SiHy contact lenses, the PAA prime coating of which is obtainedaccording to either of the dipping processes 80-1, 80-2, 80-3, 80-5 and80-6, do not show noticeable wrinkle surface patterns when examinedunder either RDIC or TDIC as described above. But, SiHy contact lenses,the PAA prime coating of which is obtained according to either of thedipping processes 80-0 and 80-4, show noticeable wrinkle surfacepatterns when examined under either RDIC or TDIC as described above.But, the winkled surface patterns have practically no adverse effectsupon the light transmissibility of the contact lenses.

Example 33

Synthesis of UV-Absorbing Amphiphilic Branched Copolymer

A 1-L jacketed reactor is equipped with 500-mL addition funnel, overheadstirring, reflux condenser with nitrogen/vacuum inlet adapter,thermometer, and sampling adapter. 89.95 g of 80% partiallyethylenically functionalized polysiloxane prepared in Example 17, A, ischarged to the reactor and then degassed under vacuum less than 1 mbarat room temperature for about 30 minutes. The monomer solution preparedby mixing 1.03 g of HEMA, 50.73 g of DMA, 2.76 g of Norblocmethacrylate, 52.07 g of TRIS, and 526.05 g of ethyl acetate is chargedto the 500-mL addition funnel followed with a degas under vacuum 100mbar at room temperature for 10 minutes and then refilled with nitrogengas. The monomer solution is degassed with same conditions foradditional two cycles. The monomer solution is then charged to thereactor. The reaction mixture is heated to 67° C. with adequatestirring. While heating, a solution composed of 2.96 g ofmercaptoethanol (chain transfer agent, CTA) and 0.72 g of dimethyl2,2′-azobis(2-methylpropionate) (V-601—initiator) and 76.90 g of ethylacetate is charged to the addition funnel followed by same degas processas the monomer solution. When the reactor temperature reaches 67° C.,the initiator/CTA solution is also added to reactor. The reaction isperformed at 67° C. for 8 hours. After the copolymerization iscompleted, reactor temperature is cooled to room temperature.

Synthesis of UV-Absorbing Amphiphilic Branched Prepolymer

The copolymer solution prepared above is ethylenically functionalized toform an amphiphilic branched prepolymer by adding 8.44 g of IEM (or2-isocyanatoethyl methacrylate in a desired molar equivalent amount) inthe presence of 0.50 g of DBTDL. The mixture is stirred at roomtemperature under a sealed condition for 24 hours. The preparedprepolymer is then stabilized with 100 ppm of hydroxy-tetramethylenepiperonyloxy before the solution is concentrated to 200 g (˜50%) andfiltered through 1 um pore size filter paper. After the reaction solventis exchanged to 1-propanol through repeated cycles of evaporation anddilution, the solution is ready to be used for formulation. The solidcontent is measured via removing the solvent at vacuum oven at 80° C.

Preparation of Lens Formulation

A lens formulation is prepared to have the following composition: 71% byweight of prepolymer prepared above; 4% by weight of DMA; 1% by weightof TPO; 1% by weight of DM PC; 1% by weight of Brij 52 fromSigma-Aldrich), and 22% by weight of 1-PrOH.

Lens Preparation

Lenses are fabricated by cast-molding of the lens formulation preparedabove using reusable mold, similar to the mold shown in FIGS. 1-6 inU.S. Pat. Nos. 7,384,590 and 7,387,759 (FIGS. 1-6) under spatiallimitation of UV irradiation. The mold comprises a female mold half madeof glass and a male mold half made of quartz. The UV irradiation sourceis a Hamamatsu lamp with a 380 nm-cut-off filter at an intensity ofabout 4.6 mW/cm². The lens formulation in the mold is irradiated with UVirradiation for about 30 seconds.

Cast-molded lenses are extracted with methyl ethyl ketone (MEK), rinsedin water, coated with polyacrylic acid (PAA) by dipping lenses in apropanol solution of PAA (0.004% by weight, acidified with formic acidto about pH 2.0), and hydrated in water.

IPC Saline is prepared from a composition containing about 0.07%PAAm-PAA and sufficient PAE to provide an initial azetidinium content ofapproximately 8.8 millimole equivalents/Liter (˜0.15% PAE) underpre-reaction conditions of 6 hrs at approximately 60° C. 5 ppm hydrogenperoxide is then added to the IPC salines to prevent bioburden growthand the IPC salines are filtered using a 0.22 micron polyether sulphone[PES] membrane filter Lenses are placed in a polypropylene lenspackaging shell with 0.6 mL of the IPC saline (half of the saline isadded prior to inserting the lens). The blister is then sealed with foiland autoclaved for 30 min at 121° C.

Lens Characterization

The obtained lenses have the following properties: E′˜0.82 MPa;DK_(c)˜159.4 (using lotrafilcon B as reference lenses, an average centerthickness of 80 μm and an intrinsic Dk 110); IP˜2.3; water %˜26.9; andUVA/UVB % T˜4.6/0.1. When observed under dark field microscope, nocracking lines are visible after rubbing the test lens. The lenses arevery lubricious in a finger rubbing test and equivalent to the controllenses.

What is claimed is:
 1. A silicone hydrogel contact lens, comprising: asilicone hydrogel bulk material covered with an outer surface hydrogellayer, wherein the silicone hydrogel bulk material comprises (i)repeating units derived from a silicone-containing vinylic monomer, asilicone-containing vinylic macromer, a silicone-containing prepolymer,or combinations thereof, and (ii) repeating units derived from ahydrophilic vinylic monomer, and has a first water content, designatedas WC_(SiHy), of from about 10% to about 70% by weight when being fullyhydrated, wherein the outer surface hydrogel layer comprises polymerchains derived from a copolymer which is a polymerization of acomposition comprising (1) 60% by weight or less of at least onereactive vinylic monomer and (2) a phosphorylcholine-containing vinylicmonomer, wherein the reactive vinylic monomer is selected from the groupconsisting of amino-C₁-C₆ alkyl (meth)acrylate, C₁-C₆ alkylamino-C₁-C₆alkyl (meth)acrylate, allylamine, vinylamine, amino-C₁-C₆ alkyl(meth)acrylamide, C₁-C₆ alkylamino-C₁-C₆ alkyl (meth)acrylamide, acrylicacid, C₁-C₄ alkylacrylic acid, N,N-2-acrylamidoglycolic acid,beta-methyl-acrylic acid, alpha-phenyl acrylic acid, beta-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid,1-carboxy-4-phenyl butadiene-1,3, itaconic acid, citraconic acid,mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaricacid, tricarboxy ethylene, and combinations thereof, and wherein theouter surface hydrogel layer is substantially free of silicone ascharacterized by having a silicon atomic percentage of 5% or less oftotal elemental percentage as measured by XPS analysis of the siliconehydrogel contact lens in dried state, wherein the silicone hydrogelcontact lens, when being fully hydrated, has: an oxygen transmissibilityof at least 40 barrers/mm; an elastic modulus (or Young's Modulus) offrom 0.3 MPa to 1.8 MPa; and an averaged water contact angle of 80degrees or less.
 2. The silicone hydrogel contact lens of claim 1,wherein the outer surface hydrogel layer is substantially free ofsilicone as characterized by having a silicon atomic percentage of 4% orless of total elemental percentage as measured by XPS analysis of thesilicone hydrogel contact lens in dried state.
 3. The silicone hydrogelcontact lens of claim 2, wherein the outer surface hydrogel layer has athickness of at least about 0.1 μm.
 4. The silicone hydrogel contactlens of claim 2, wherein the outer surface hydrogel layer has athickness of from about 0.25 μm to about 15 μm.
 5. The silicone hydrogelcontact lens of claim 1, wherein the outer surface hydrogel layer has athickness of from about 0.5 μm to about 12.5 μm.
 6. The siliconehydrogel contact lens of claim 5, wherein the outer surface hydrogellayer has a water-swelling ratio of at least about 150%.
 7. The siliconehydrogel contact lens of claim 1, wherein the outer surface hydrogellayer has a thickness of from about 1 μm to about 10 μm.
 8. The siliconehydrogel contact lens of claim 7, wherein the outer surface hydrogellayer has a water-swelling ratio of at least about 150%.
 9. The siliconehydrogel contact lens of claim 1, wherein the reactive vinylic monomeris selected from the group consisting of amino-C₁-C₆ alkyl(meth)acrylate, C₁-C₆ alkylamino-C₁-C₆ alkyl (meth)acrylate, allylamine,vinylamine, amino-C₁-C₆ alkyl (meth)acrylamide, C₁-C₆ alkylamino-C₁-C₆alkyl (meth)acrylamide, acrylic acid, C₁-C₄ alkylacrylic acid,N,N-2-acrylamidoglycolic acid, and combinations thereof.
 10. Thesilicone hydrogel contact lens of claim 9 wherein the silicone hydrogelbulk material comprises repeating units derived from asilicone-containing vinylic monomer selected from the group consistingof N-[tris(trimethylsiloxy)silylpropyl]-(meth)acrylamide,N-[tris(dimethylpropylsiloxy)-silylpropyl]-(meth)acrylamide,N-[tris(dimethylphenylsiloxy)silylpropyl] (meth)acrylamide,N-[tris(dimethylethylsiloxy)silylpropyl] (meth)acrylamide,N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)-2-methylacrylamide;N-(2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl)acrylamide;N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl]-2-methylacrylamide;N,N-bis[2-hydroxy-3-(3-(bis(trimethylsilyloxy)methylsilyl)propyloxy)propyl] acrylamide;N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)-2-methylacrylamide;N-(2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl)acrylamide;N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]-2-methylacrylamide;N,N-bis[2-hydroxy-3-(3-(tris(trimethylsilyloxy)silyl)propyloxy)propyl]acrylamide;N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]-2-methylacrylamide;N-[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide;N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl) propyloxy)propyl]-2-methylacrylamide;N,N-bis[2-hydroxy-3-(3-(t-butyldimethylsilyl)propyloxy)propyl]acrylamide;3-methacryloxy propylpentamethyldisiloxane,tris(trimethylsilyloxy)silylpropyl methacrylate (TRIS),(3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane),(3-methacryloxy-2-hydroxpropyloxy)propyltris(trimethylsiloxy)silane,3-methacryloxy-2-(2-hydroxyethoxy)-propyloxy)propylbis(trimethylsiloxy)methylsilane,N-2-methacryloxyethyl-O-(methyl-bis-trimethylsiloxy-3-propyl)silylcarbamate, 3-(trimethylsilyl)propylvinyl carbonate,3-(vinyloxycarbonylthio)propyl-tris(trimethyl-siloxy)silane,3-[tris(trimethylsiloxy)silyl]propylvinyl carbamate,3-[tris(trimethylsiloxy)silyl] propyl allyl carbamate,3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate,t-butyldimethyl-siloxyethyl vinyl carbonate; trimethylsilylethyl vinylcarbonate, trimethylsilylmethyl vinyl carbonate, and combinationsthereof.
 11. The silicone hydrogel contact lens of claim 9, wherein thesilicone hydrogel bulk material comprises: (i) repeating units derivedfrom a polysiloxane vinylic monomer, a polysiloxane vinylic macromer, orcombinations thereof; and (ii) repeating units derived from ahydrophilic vinylic monomer selected from the group consisting ofN,N-dimethylacrylamide, N,N-dimethylmethacrylamide, 2-acrylamidoglycolicacid, 3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,1-n-propyl-3-methylene-2-pyrrolidone,1-n-propyl-5-methylene-2-pyrrolidone,1-isopropyl-3-methylene-2-pyrrolidone,1-isopropyl-5-methylene-2-pyrrolidone,1-n-butyl-3-methylene-2-pyrrolidone,1-tert-butyl-3-methylene-2-pyrrolidone, 2-hydroxyethylmethacrylate,2-hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropylmethacrylate, trimethylammonium 2-hydroxy propylmethacrylatehydrochloride, aminopropyl methacrylate hydrochloride,dimethylaminoethyl methacrylate, glycerol methacrylate,N-vinyl-2-pyrrolidone, allyl alcohol, vinylpyridine, a C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 1500, methacrylic acid, N-vinyl formamide, N-vinylacetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, N-vinylcaprolactam, and mixtures thereof.
 12. The silicone hydrogel contactlens of claim 11, wherein the silicone hydrogel bulk material furthercomprises repeating units derived from a crosslinking agent.
 13. Thesilicone hydrogel contact lens of claim 12, wherein the crosslinkingagent is selected from the group consisting of tetraethyleneglycoldiacrylate, triethyleneglycol diacrylate, ethyleneglycol diacylate,diethyleneglycol diacrylate, tetraethyleneglycol dimethacrylate,triethyleneglycol dimethacrylate, ethyleneglycol dimethacylate,diethyleneglycol dimethacrylate, trimethylopropane trimethacrylate,pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinylmethacrylate, ethylenediamine dimethyacrylamide, ethylenediaminediacrylamide, glycerol dimethacrylate, triallyl isocyanurate, triallylcyanurate, allylmethacrylate, allylmethacrylate,1,3-bis(methacrylamidopropyI)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane,N,N′-methylenebisacrylamide, N,N′-methylenebismethacrylamide,N,N′-ethylenebisacrylamide, N,N′-ethylenebismethacrylamide,1,3-bis(N-methacrylamidopropyI)-1,1,3,3-tetrakis-(trimethylsiloxy)disiloxane,1,3-bis(methacrylamidobutyl)-1,1,3,3-tetrakis(trimethylsiloxy)-disiloxane,1,3-bis(acrylamidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane,1,3-bis(methacryloxyethylureidopropyl)-1,1,3,3-tetrakis(trimethylsiloxy)disiloxane,and combinations thereof.
 14. The silicone hydrogel contact lens ofclaim 12, wherein the silicone hydrogel bulk material further comprisesa UV-absorbing agent, a visibility tinting agent, an antimicrobialagent, a bioactive agent, a leachable lubricant, a leachabletear-stabilizing agent, or a mixture thereof.
 15. The silicone hydrogelcontact lens of claim 14, wherein the outer surface hydrogel layer issubstantially free of silicone as characterized by having a siliconatomic percentage of 4% or less of total elemental percentage asmeasured by XPS analysis of the silicone hydrogel contact lens in driedstate.
 16. The silicone hydrogel contact lens of claim 15, wherein theouter surface hydrogel layer has a thickness of at least about 0.1 μm.17. The silicone hydrogel contact lens of claim 14, wherein the outersurface hydrogel layer has a thickness of from 0.25 μm to 15 μm.
 18. Thesilicone hydrogel contact lens of claim 14, wherein the outer surfacehydrogel layer has a thickness of from 0.5 μm to 12.5 μm.
 19. Thesilicone hydrogel contact lens of claim 18, wherein the outer surfacehydrogel layer has a water-swelling ratio of at least about 150%. 20.The silicone hydrogel contact lens of claim 14, wherein the outersurface hydrogel layer has a thickness of from 1 μm to 10 μm.
 21. Thesilicone hydrogel contact lens of claim 20, wherein the outer surfacehydrogel layer has a water-swelling ratio of at least about 150%. 22.The silicone hydrogel contact lens of claim 1, wherein when being fullyhydrated the silicone hydrogel contact lens has a surface hydrophilicitycharacterized by having a water breakup time of at least 10 seconds andan averaged water contact angle of 70 degrees or less.
 23. The siliconehydrogel contact lens of claim 15, wherein when being fully hydrated thesilicone hydrogel contact lens has a surface hydrophilicitycharacterized by having a water breakup time of at least 10 seconds andan averaged water contact angle of 70 degrees or less.